https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Tyler+Marcinko 2026-09-15T04:06:35Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102899 2014-12-11T20:07:28Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble dimers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/141211_h13f/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The &lt;scene name='38/389965/141211_p32a/3'&gt;P32A&lt;/scene&gt; mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment is minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102898 2014-12-11T20:03:06Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble dimers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/141211_h13f/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The &lt;scene name='38/389965/141211_p32a/3'&gt;P32A&lt;/scene&gt; mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102897 2014-12-11T19:56:09Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble dimers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The &lt;scene name='38/389965/141211_p32a/3'&gt;P32A&lt;/scene&gt; mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102896 2014-12-11T19:49:16Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble dimers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The &lt;scene name='38/389965/141211_p32a/2'&gt;P32A&lt;/scene&gt; mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102895 2014-12-11T19:44:14Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble dimers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The &lt;scene name='38/389965/141211_p32a/1'&gt;P32A&lt;/scene&gt; mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102894 2014-12-11T19:37:48Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble dimers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The &lt;scene name='38/389965/P32a_alt_dimer/3'&gt;P32A&lt;/scene&gt; mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102893 2014-12-11T19:26:46Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble dimers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_alt_dimer/3'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102892 2014-12-11T19:18:54Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble dimers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_test/1'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102891 2014-12-11T14:12:14Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_test/1'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102795 2014-12-10T21:23:50Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_test/1'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102793 2014-12-10T20:44:31Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_tetramer2/1'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102792 2014-12-10T20:37:04Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_tetramer/1'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102790 2014-12-10T20:13:17Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/H13f_hexamer/1'&gt;H13F&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_alt_dimer/2'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102789 2014-12-10T19:56:24Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/Hexamer_with_copper/2'&gt;H13F mutant&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_alt_dimer/2'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure &lt;ref&gt;3&lt;/ref&gt;.<br /> <br /> The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics &lt;ref&gt;4&lt;/ref&gt;.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]<br /> <br /> 4. [http://www.ncbi.nlm.nih.gov/pubmed/?term=Capillary+electrophoresis+investigation+of+a+partially+unfolded+conformation+of+β2-microglobulin De Lorenzi, E., Grossi, S., Massolini, G., Giorgetti, S., Mangione, P., Andreola, A., Chiti, F., Belloti, V., Caccialanza, G. (2002) Electrophoresis. 23, 918-925.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102788 2014-12-10T19:14:24Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/Hexamer_with_copper/2'&gt;H13F mutant&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_alt_dimer/2'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure. &lt;ref&gt;3&lt;/ref&gt;<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102786 2014-12-10T19:13:52Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/Hexamer_with_copper/2'&gt;H13F mutant&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_alt_dimer/2'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure. &lt;ref&gt;3&lt;/ref&gt;<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102785 2014-12-10T19:07:23Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/Hexamer_with_copper/2'&gt;H13F mutant&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='38/389965/P32a_alt_dimer/1'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure. &lt;ref&gt;3&lt;/ref&gt;<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102783 2014-12-10T18:55:56Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/Hexamer_with_copper/2'&gt;H13F mutant&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m.&lt;ref&gt;3&lt;/ref&gt;<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]<br /> <br /> 3. [http://www.ncbi.nlm.nih.gov/pubmed/16491088?dopt=Abstract Eakin, C.M., Berman, A.J., and Miranker, A.D. (2006) Nat. Struct. Mol. Biol. 13, 202-208.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102782 2014-12-10T18:53:20Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/Hexamer_with_copper/2'&gt;H13F mutant&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102781 2014-12-10T18:44:38Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='38/389965/Hexamer_with_copper/2'&gt;H13F mutant&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2101549 2014-12-10T16:35:15Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members &lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H13F mutant&lt;/scene&gt; of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers &lt;ref&gt;2&lt;/ref&gt;.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]<br /> <br /> 2. [http://www.ncbi.nlm.nih.gov/pubmed/19172750?dopt=Abstract Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D. (2008) Nat. Struct. Mol. Biol. 15, 965-971.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2101428 2014-12-10T16:27:17Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members&lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H13F mutant&lt;/scene&gt; form of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2101210 2014-12-10T16:20:34Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members&lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> 1. [http://www.pnas.org/content/99/15/9771.full.pdf+html Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.]</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2100953 2014-12-10T16:12:36Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members&lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> {{Reflist}}Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2100911 2014-12-10T16:11:29Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members&lt;ref&gt;1&lt;/ref&gt;. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==<br /> &lt;ref&gt;Saper, M. A., Bjorkman, P. J. &amp; Wiley, D. C. (1991) J. Mol. Biol. 219, 277–319.&lt;/ref&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2100518 2014-12-10T16:01:27Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='60/609778/B-sandwich/1'&gt;single disulfide bond and a seven-stranded B-sandwich motif&lt;/scene&gt; common to immunoglobulin family members. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2100401 2014-12-10T15:58:22Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2100372 2014-12-10T15:56:57Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='38/389965/B-sandwich_disulfide/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2100182 2014-12-10T15:47:11Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (β2m) is a structural protein sub-unit of the class I major histocompatibility complex. β2m is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='60/609778/B-sandwich/1'&gt;single disulfide bond and a seven-stranded β-sandwich motif&lt;/scene&gt; common to immunoglobulin family members. In dialysis patients, β2m has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2100063 2014-12-10T15:40:26Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='60/609778/B-sandwich/1'&gt;single disulfide bond and a seven-stranded B-sandwich motif&lt;/scene&gt; common to immunoglobulin family members. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as [https://en.wikipedia.org/wiki/Haemodialysis-associated_amyloidosis dialysis-related amyloidosis (DRA)]. The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2100018 2014-12-10T15:37:45Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It is composed of 99 amino acids and has a molecular weight of approximately 12 kDa. Structurally, it features a &lt;scene name='60/609778/B-sandwich/1'&gt;single disulfide bond and a seven-stranded B-sandwich motif&lt;/scene&gt; common to immunoglobulin family members. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2099811 2014-12-10T15:25:23Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> ==References==</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2099757 2014-12-10T15:22:22Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == Elucidating Early Aggregation Events ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> ==Additional Resources==<br /> For additional information, see: [[Metabolic Disorders]]<br /> &lt;br /&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=CBI_Molecules&diff=2099622 2014-12-10T15:13:23Z

<p>Tyler Marcinko: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground] (see also [[Molecular Playground|Molecular Playground in Proteopedia]]). Follow the links below to read nontechnical descriptions, in Proteopedia, of these molecules.<br /> <br /> UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.<br /> <br /> Fall 2014: CBI Molecules are due 12/3/14 and should be added at the TOP of the list from your lab. Label it as &quot;in progress&quot; until you are finished, and then as &quot;New 2014&quot; or &quot;Revised 2014&quot;. For those editing an existing CBI Molecule, start by making a copy of that entry (leaving the original intact) so that it retains the full author list of all authors that contributed (or include credits and a link to the original page and authors if it does not).<br /> Follow the instructions at the bottom of this page.<br /> <br /> <br /> ==Molecules==<br /> '''** Designates CBI Molecules Featured on [http://www.umass.edu/cbi/ CBI website]'''<br /> <br /> [http://chamberslab.com/wp/ Chambers Lab]<br /> <br /> : '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano<br /> <br /> <br /> [http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]<br /> <br /> : '''[[Molecular Playground/ClyA]]''', Bib Yang<br /> : '''[[Molecular Playground/OmpG]]''', Christina Chisholm<br /> <br /> <br /> [http://openwetware.org/wiki/Chien Chien Lab]<br /> <br /> : '''[[Molecular Playground/ClpP]]''', Lisa Hernandez, Rob Vass '''New 2014'''<br /> : '''[[Molecular Playground/Homo-dimeric RcdA]]''', Kamal K. Joshi <br /> : **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau '''Best CBI Molecule 2011'''<br /> : '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu<br /> <br /> <br /> Farkas Lab<br /> : '''[[Molecular Playground/CLOCK:BMAL1 heterodimer complex]]''', Hui-Hsien Lin, Joseph Hardie, Michael Mingroni '''New 2014''' <br /> <br /> Forbes Lab<br /> <br /> : '''[[Molecular Playground/CheR]]''', Miaomin Zhang<br /> : '''[[Molecular Playground/RBP]]''', Jan Panteli<br /> : '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> <br /> [http://www.biochem.umass.edu/garman/index.html Garman Lab]<br /> <br /> : '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> : '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli<br /> <br /> <br /> [http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]<br /> <br /> : '''[[Molecular_Playground/DnaK]]''', Joseph Tilitsky, New 2014<br /> : '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy '''Best Overall CBI Molecule 2010'''<br /> : '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez<br /> : **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani '''Best CBI Molecule 2012'''<br /> <br /> <br /> [http://people.chem.umass.edu/jhardy/ Hardy Lab]<br /> <br /> : '''[[Molecular Playground/Executioner Caspase-7]]''', Derek MacPherson, Maureen E. Hill<br /> : '''[[Molecular Playground/Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao<br /> : '''[[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay<br /> : '''[[Molecular Playground/Caspase-7 Dynamics]]'''<br /> : '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber<br /> : '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez<br /> : '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls<br /> : '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz<br /> <br /> <br /> Hebert Lab<br /> <br /> : '''[[Molecular_Playground/Hsp70-Hsp90]]''', Jill Graham<br /> : '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben<br /> : '''[[Molecular Playground/Saposin C]]''', Abla Tannous<br /> : '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd<br /> <br /> <br /> [http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]<br /> <br /> : '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez, Yuzhou Tang<br /> <br /> <br /> [http://people.chem.umass.edu/mholden/ Holden Lab]<br /> <br /> : '''[[Molecular Playground/Protective Antigen]]''', Jing Huang<br /> <br /> <br /> [http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]<br /> <br /> : '''[http://proteopedia.org/wiki/index.php/Chengfeng_Ren Molecular Playground/Inteferon]'''[Revised], Chengfeng Ren<br /> : ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski<br /> : '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita<br /> : '''[[Molecular Playground/Antithrombin-Heparin]]''', Yunlong Zhao<br /> <br /> <br /> [http://people.chem.umass.edu/knapplab/?q=knappchem/index.html/ Knapp Lab]<br /> : '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas '''Best CBI Molecule Proteopedia Page 2010''' '''***New Fall 2014***'''<br /> : '''[[Molecular Playground/FIH]]''', Vanessa Chaplin, Cornelius Taabazuing, Breanne Holmes, John Hangasky<br /> <br /> <br /> <br /> <br /> [http://people.chem.umass.edu/mmaroney/ Maroney Lab]<br /> <br /> : '''[[Molecular Playground/UreE]]''', Priyanka Basak, '''New 2014'''<br /> : '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr<br /> : '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr, Hsin-Ting (Tiffany )Huang, '''Revised 2014'''<br /> : '''[[Molecular Playground/HypA]]''', Heidi Hu<br /> <br /> <br /> [http://www.chem.umass.edu/~cmartin/ Martin Lab]<br /> <br /> : **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia '''Best CBI Molecule 2011'''<br /> : '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia<br /> : '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan <br /> <br /> <br /> [http://www.peytonlab.org/ Peyton Lab]<br /> : '''[[Molecular Playground/IntegrinBeta1]]''', Lauren Jansen, Lauren Barney, Elizabeth Brooks, Alyssa Schwartz ***'''NEW FALL 2014''''***<br /> : '''[[Molecular Playground/MMP14]]''', Lauren Jansen<br /> : '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen<br /> : '''[[Molecular Playground/FAK]]''', Dannielle Ryman<br /> <br /> [http://roberts.openwetware.org/ Roberts Lab]<br /> <br /> : '''[[Molecular Playground/Taxol]]''', Elizabeth Cummings, Rohan Patil, Sarah Wilson ***'''Revised Fall 2014'''***<br /> : '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> <br /> [http://www.umass.edu/rotellogroup/ Rotello Lab]<br /> <br /> : '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino<br /> : '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang<br /> : '''[[Molecular playground/Chymotrypsin]]''', Brad<br /> : '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell<br /> <br /> <br /> [http://http://www.umass.edu/schiffman/ Schiffman Lab]<br /> : '''[[Molecular Playground/Streptavidin]]''', Katrina Rieger<br /> <br /> <br /> [http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]<br /> : '''[[Molecular Playground/Tic40]]''', Mine Canakci<br /> <br /> <br /> Tew Lab<br /> <br /> : '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde<br /> <br /> <br /> Thayumanavan Lab<br /> : '''[[Interleukin-1 beta]]''', Huan He<br /> : '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez<br /> : '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> : '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> : '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> : '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado <br /> : '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang<br /> : ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo<br /> : '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko<br /> <br /> <br /> Thayumanavan &amp; Vachet Labs<br /> <br /> : '''[[Molecular Playground/Trypsin]]''', Gladys Murage<br /> <br /> <br /> [http://people.chem.umass.edu/thompson/index.html Thompson Lab]<br /> <br /> : '''[[Molecular Playground/Bacterial Chemotaxis Complex]]''', Elizabeth R. Haglin, Maryam Kashefi<br /> : '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin<br /> : '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones<br /> : '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li<br /> <br /> <br /> [http://www.chem.umass.edu/~vachet/index.html Vachet Lab]<br /> <br /> : '''[[Molecular Playground/Human Serum Albumin]]''', Mahalia Serrano ''*Revised 2014*''<br /> : '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto, Tyler Marcinko ***'''Revised Fall 2014'''*** '''Best CBI Molecule Jmol scenes 2010'''<br /> : '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou <br /> :'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne<br /> : '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang<br /> <br /> <br /> Other Molecules of interest<br /> <br /> : '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]<br /> <br /> <br /> Other Laboratories<br /> <br /> :'''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey, Schnarr lab<br /> : '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey, Schnarr lab<br /> : '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad, Schnarr lab<br /> <br /> : '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang, Weis lab<br /> <br /> : '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffi, Bhatia Lab<br /> : '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer, Bhatia Lab<br /> <br /> : '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]<br /> <br /> : '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab<br /> <br /> : '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab<br /> <br /> ==Instructions==<br /> <br /> '''The goal is for students to work collaboratively to create one excellent CBI Molecule for each CBI research group, to be featured on the CBI website.'''<br /> <br /> Fall 2014: Complete steps 1-3 before the CBI Molecule Workshop on 11/19; bring your computer to the CBI Molecule Workshop in ISB 321. You will be able to start work on your CBI Molecule at the workshop. You should plan to stay and finish your molecule after the workshop (or as soon as possible) while the instructions and ideas are fresh in your mind.<br /> <br /> A successful CBI Molecule is an interesting, nontechnical description of a molecule related to your group's research. It should tell an interesting story with few words and many green scenes. Green scenes should be clear and attractive illustrations that tell your story. It's great if you can end with a brief statement about how it relates to your group's research goals.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. <br /> <br /> 2. Read through the rest of the instructions, do the tutorials below, and look at any existing CBI Molecules from your research group. Talk with other CBI students in your research group and decide how you will collaborate to make an improved CBI Molecule related to your group's research. Develop ideas for the scenes that each of you will make.<br /> <br /> 3. Get started working in Proteopedia. Make yourself a sandbox page: Enter &quot;User:Your Name/Sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. Practice entering text, inserting a structure window with scrolling text (green 4-square button on the right), and creating a green scene. Explore the HELP links below to learn how to make a green scene. You can look at other Proteopedia pages in edit mode to see how different effects (like colored text) are achieved (but this won't show you how the scene effects are made). <br /> <br /> '''Complete the above steps before the CBI Molecule Workshop.'''<br /> <br /> 4. When editing an existing CBI Molecule, leave the original intact and make a copy that you will edit so that it retains the full author list of all authors that contributed. You are encouraged to collaborate on the CBI Molecules, but everyone will need to log in as themself and create a green scene to get credit for their work and to appear as authors on the final list. If you are the sole student from your group enrolled in Chalk Talk and have not previously made a CBI Molecule, try to convince another group member who has previously made a CBI Molecule (see list above) to join us for the workshop so that you can work together.<br /> <br /> 5. Your final pages should be called &quot;Molecular Playground/your molecule&quot; and should have links on this CBI Molecule page -- put the new ones first on the list from your research group. Label them &quot;in progress&quot; until you are finished, and then &quot;new 2014&quot; or &quot;revised 2014&quot;. Minimize text; tell your story with green scenes!<br /> <br /> 6. When your CBI Molecule is complete, send Lynmarie an email to nominate a cool scene/clever caption you would like to feature at the Molecular Playground (include a link to your CBI Molecule, name of the green scene, and caption).<br /> <br /> ==Links to HELP pages==<br /> Overview at [[Help:Contents ]]<br /> <br /> See also [[Help:Getting_Started_in_Proteopedia]] <br /> <br /> Videos showing how to use Proteopedia:<br /> [[Proteopedia:Video_Guide]]<br /> (Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)<br /> <br /> [[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]<br /> gives succinct step by step instructions on how to create a molecular scene.<br /> <br /> A powerpoint-like set of slides that walks a user through the process of creating a new page and a new molecular scene/green link.<br /> [http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]<br /> <br /> [[Proteopedia:Guidelines for Ethical Writing]].<br /> Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.<br /> <br /> For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2075935 2014-12-04T17:17:11Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2075932 2014-12-04T16:43:46Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillization are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2075931 2014-12-04T16:43:05Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2075930 2014-12-04T16:34:30Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2071442 2014-11-29T21:13:31Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils (citations). In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Notably,<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2071441 2014-11-29T21:09:06Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils (citations). In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Notably,<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> The dimer of &lt;scene name='60/609778/P32a/2'&gt;P32A&lt;/scene&gt; has proved to be useful in determining the importance of the cis-trans isomerization of the proline residue.<br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2071440 2014-11-29T21:01:42Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils (citations). In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Notably,<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the structure of the hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers.<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2071439 2014-11-29T20:59:43Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils (citations). In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Notably,<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2071438 2014-11-29T20:55:55Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils (citations). In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Notably,<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The &lt;scene name='60/609778/H31f/1'&gt;H31F mutant&lt;/scene&gt; form of B2m has permitted the crystal structure of the hexamer be solved. However, this mutant of B2m does not progress to form amyloid fibrils and instead forms off-pathway oligomers.<br /> <br /> Another important variant of B2m is <br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2071435 2014-11-29T20:21:44Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils (citations). In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Soluble oligomers then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Notably,<br /> <br /> == B2m Mutations ==<br /> <br /> There have been several mutants of B2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis.<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2071434 2014-11-29T19:20:31Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin (B2m) is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> There are several processes that can cause B2m to aggregate and ultimately form amyloid fibrils (citations). In the copper-catalyzed pathway, the process begins with the formation of a homodimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Display Nick's Dimer, try to find the tetramer, and the hexameter<br /> <br /> == B2m Mutations ==<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2065806 2014-11-20T17:38:26Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> Fibril Assembly begins with the formation of a Dimer. Dimer formation is initiated when copper binds near the &lt;scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'&gt;N-terminus&lt;/scene&gt;. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent &lt;scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'&gt;Dimer&lt;/scene&gt;.<br /> <br /> Display Nick's Dimer, try to find the tetramer, and the hexameter<br /> <br /> == B2m Mutations ==<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2065805 2014-11-20T17:26:40Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 micro globulin with Na+ ion bound - PDB: 1LDS' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> Display Nick's Dimer, try to find the tetramer, and the hexameter<br /> <br /> == B2m Mutations ==<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2065804 2014-11-20T16:57:05Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 microglobulin' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The mechanism of oligomerization and eventual fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> Display Nick's Dimer, try to find the tetramer, and the hexameter<br /> <br /> == B2m Mutations ==<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2065803 2014-11-20T16:56:25Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 microglobulin' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin is a structural protein sub-unit of the class I major histocompatibility complex. It has a molecular weight of approximately 12 kDa. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA). The oligomerization mechanisms and fibrillation are of particular interest to the Vachet Research Group at the University of Massachusetts-Amherst.<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> Display Nick's Dimer, try to find the tetramer, and the hexameter<br /> <br /> == B2m Mutations ==<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Code to color a green scene ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko https://proteopedia.org/index.php?title=Tyler_marcinko/sandbox_1&diff=2065643 2014-11-19T18:15:57Z

<p>Tyler Marcinko: </p> <hr /> <div>&lt;Structure load='1LDS' size='400' frame='true' align='right' caption='Human Beta-2 microglobulin' scene='Insert optional scene name here' /&gt;<br /> <br /> == Beta-2-microglobulin==<br /> Beta-2 microglobulin is a 12 kDa protein sub-unit of the class I major histocompatibility complex. In dialysis patients, it has the propensity to form amyloid fibrils in a condition known as dialysis-related amyloidosis (DRA).<br /> <br /> == Function ==<br /> <br /> == Disease ==<br /> <br /> == Aggregation Mechanism ==<br /> <br /> Display Nick's Dimer, try to find the tetramer, and the hexameter<br /> <br /> == B2m Mutations ==<br /> <br /> Structural effects of the various mutations and their oligomers<br /> <br /> == Structural highlights ==<br /> <br /> This is a sample scene created with SAT to &lt;scene name=&quot;/12/3456/Sample/1&quot;&gt;color&lt;/scene&gt; by Group, and another to make &lt;scene name=&quot;/12/3456/Sample/2&quot;&gt;a transparent representation&lt;/scene&gt; of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> &lt;/StructureSection&gt;<br /> <br /> <br /> == Useful Links ==<br /> <br /> The Vachet Lab [http://www.chem.umass.edu/~vachet/]<br /> <br /> == References ==<br /> &lt;references/&gt;</div>

Tyler Marcinko