Sandbox Reserved 1786: Difference between revisions

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The constant region of IgM is made up of the two <scene name='95/952714/Heavy_chain/1'>heavy chains</scene>. These heavy chains form a bridge connecting the FAB region or variable region to the transmembrane region (Figure 1). They also act as a wire that the variable region can send a signal through to the transmembrane region as a mechanical change.

<scene name='95/952715/Extracellular_transmembrane_v2/10'>Extracellular transmembrane interactions</scene> help hold the heavy chains and Igα/Igβ chains together in the extracellular portion of the transmembrane region.

<scene name='95/952715/Extracellular_transmembrane_v2/10'>Extracellular transmembrane interactions</scene> help hold the heavy chains and Igα/Igβ chains together in the extracellular portion of the transmembrane region. Because a conformational change occurs throughout the entirety of the IgM-BCR complex, the Fc region must be able to tolerate the contortion of the structure as the antigen binds. In constant region two, which is located at the start of the Fc region, '''{{Font color|violet|heavy chain A}}''' and heavy chain B make a <scene name='95/952713/Disulfides/5'>disulfide bridge</scene> to stabilize the IgM-BCR and drive downstream signaling.

Because a conformational change occurs throughout the entirety of the IgM-BCR complex, the Fc region must be able to tolerate the contortion of the ~~molecule~~ as the antigen binds. In constant region two, which is located at the start of the Fc region, '''{{Font color|violet|heavy chain A}}''' and heavy chain B make a <scene name='95/952713/Disulfides/5'>disulfide bridge</scene> to stabilize the IgM-BCR and drive downstream signaling.

To maximize the Fc region’s signal transduction efficiency and Van der Waals contacts, constant region two of '''{{Font color|violet|heavy chain A}}''' makes an asymmetrical association with constant region three of heavy chain B to create a <scene name='95/952713/Trans_heavy/7'>heavy chain interface</scene>. More specifically, Arg243 and Arg251 residues from '''{{Font color|violet|heavy chain A}}''' donate three hydrogen bonds to Leu433, Thr431, and Asp376 residues on heavy chain B. Furthermore, Leu313 of heavy chain A accepts a hydrogen bond from Thr429 on heavy chain B. <ref name="Ma">PMID:35981028</ref>

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===Fab Region===

The Fab region of the antibody is where antigen recognition occurs upon binding (Figure 1). On each arm is one heavy ('''{{Font color|violet|A}}'''/B) and one light (A/B) chain, both containing domains identical to their respective counterparts. Repeats of β-sandwiches form the [https://en.wikipedia.org/wiki/Antibody constant and variable domains] within the Fab region ~~as antigen~~ recognition occurs at the variable domain while the constant domain connects it to the rest of the IgM complex. Because the Fab region of IgM is poorly resolved, a structural analysis of an HIV neutralizing antibody called VCR01 was performed to approximate where an antigen would bind to at the <scene name='95/952714/Variable_region/1'>variable region</scene>. <ref name="Zhou">PMID:20616231</ref>

The Fab region of the antibody is where antigen recognition occurs upon binding (Figure 1). On each arm is one heavy ('''{{Font color|violet|A}}'''/B) and one light (A/B) chain, both containing domains identical to their respective counterparts. Repeats of β-sandwiches form the [https://en.wikipedia.org/wiki/Antibody constant and variable domains] within the Fab region. Antigen recognition occurs at the variable domain while the constant domain connects it to the rest of the IgM complex. Because the Fab region of IgM is poorly resolved, a structural analysis of an HIV neutralizing antibody called VCR01 was performed to approximate where an antigen would bind to at the <scene name='95/952714/Variable_region/1'>variable region</scene>. <ref name="Zhou">PMID:20616231</ref>

The IgM-BCR contains areas referred to as [https://en.wikipedia.org/wiki/Complementarity-determining_region complementary-determining regions](CDRs), which are where the antigen makes <scene name='95/952713/Antigen_antibody_contact/2'>contact</scene> with the antibody on the Fab domain. Figure 2 depicts this as a surface representation given that the specific residues within the antigen-binding motif are unknown.

Due to the poor resolution of the Fab region, specific side chain interactions between the heavy ('''{{Font color|violet|A}}'''/B) and light (A/B) chains have not been determined. It is estimated that each β-sandwich contains one disulfide bridge with additional hydrogen bonds. The <scene name='95/952713/Heavy-light_chain_interface/2'>heavy-light chain interface</scene> shows how the four heavy and light chain β-sandwiches fit together. The Fab region heavy chains attach to the Fc region heavy chains, before continuing down into the intracellular domain to interact with the Igα/Igβ subunits. The light chains (A/B) however are only connected to the heavy chains ('''{{Font color|violet|A}}'''/B) within the Fab region, thus have no contact with the Igα/Igβ heterodimer.

Due to the poor resolution of the Fab region, specific side chain interactions between the heavy ('''{{Font color|violet|A}}'''/B) and light (A/B) chains have not been determined. Based on the general structure of an [https://en.wikipedia.org/wiki/Antibody antibody] it is estimated that each β-sandwich contains one disulfide bridge with additional hydrogen bonds. The <scene name='95/952713/Heavy-light_chain_interface/2'>heavy-light chain interface</scene> shows how the four heavy and light chain β-sandwiches fit together. The Fab region heavy chains attach to the Fc region heavy chains, before continuing down into the intracellular domain to interact with the Igα/Igβ subunits. The light chains (A/B) however are only connected to the heavy chains ('''{{Font color|violet|A}}'''/B) within the Fab region, thus have no contact with the Igα/Igβ heterodimer.

[[Image:IgM_Surface2.png|400 px|left|thumb|'''Figure 3. Surface Representation of IgM Antibody Binding Pocket.''' On one arm of the IgM antibody, the antigen makes contact with light chain A at the L1 and L3 complementary-determining regions. Furthermore, it makes contact with heavy chain A at the H1, H2, and H3 complementary-determining regions. The location of the complementary-determining regions were approximated using the structure of the VCR01 variable region and were visualized using PyMOL.]]

Sandbox Reserved 1786: Difference between revisions

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@@ Line 36: / Line 36: @@
 The constant region of IgM is made up of the two <scene name='95/952714/Heavy_chain/1'>heavy chains</scene>. These heavy chains form a bridge connecting the FAB region or variable region to the transmembrane region (Figure 1). They also act as a wire that the variable region can send a signal through to the transmembrane region as a mechanical change.
-<scene name='95/952715/Extracellular_transmembrane_v2/10'>Extracellular transmembrane interactions</scene> help hold the heavy chains and <b><span class="text-brown">Igα</span></b>/<b><span class="text-orange">Igβ</span></b> chains together in the extracellular portion of the transmembrane region.
+<scene name='95/952715/Extracellular_transmembrane_v2/10'>Extracellular transmembrane interactions</scene> help hold the heavy chains and <b><span class="text-brown">Igα</span></b>/<b><span class="text-orange">Igβ</span></b> chains together in the extracellular portion of the transmembrane region. Because a conformational change occurs throughout the entirety of the IgM-BCR complex, the Fc region must be able to tolerate the contortion of the structure as the antigen binds. In constant region two, which is located at the start of the Fc region, '''{{Font color|violet|heavy chain A}}''' and <b><span class="text-blue">heavy chain B</span></b> make a <scene name='95/952713/Disulfides/5'>disulfide bridge</scene> to stabilize the IgM-BCR and drive downstream signaling.
-Because a conformational change occurs throughout the entirety of the IgM-BCR complex, the Fc region must be able to tolerate the contortion of the molecule as the antigen binds. In constant region two, which is located at the start of the Fc region, '''{{Font color|violet|heavy chain A}}''' and <b><span class="text-blue">heavy chain B</span></b> make a <scene name='95/952713/Disulfides/5'>disulfide bridge</scene> to stabilize the IgM-BCR and drive downstream signaling.
 To maximize the Fc region’s signal transduction efficiency and Van der Waals contacts, constant region two of '''{{Font color|violet|heavy chain A}}''' makes an asymmetrical association with constant region three of <b><span class="text-blue">heavy chain B</span></b> to create a <scene name='95/952713/Trans_heavy/7'>heavy chain interface</scene>. More specifically, Arg243 and Arg251 residues from '''{{Font color|violet|heavy chain A}}''' donate three hydrogen bonds to Leu433, Thr431, and Asp376 residues on <b><span class="text-blue">heavy chain B</span></b>. Furthermore, Leu313 of heavy chain A accepts a hydrogen bond from Thr429 on heavy chain B. <ref name="Ma">PMID:35981028</ref>
@@ Line 46: / Line 44: @@
 ===Fab Region===
-The Fab region of the antibody is where antigen recognition occurs upon binding (Figure 1). On each arm is one heavy ('''{{Font color|violet|A}}'''/<b><span class="text-blue">B</span></b>) and one light (<b><span class="text-purple">A</span></b>/<b><span class="text-cyan">B</span></b>) chain, both containing domains identical to their respective counterparts. Repeats of β-sandwiches form the [https://en.wikipedia.org/wiki/Antibody constant and variable domains] within the Fab region as antigen recognition occurs at the variable domain while the constant domain connects it to the rest of the IgM complex. Because the Fab region of IgM is poorly resolved, a structural analysis of an HIV neutralizing antibody called VCR01 was performed to approximate where an antigen would bind to at the  <scene name='95/952714/Variable_region/1'>variable region</scene>. <ref name="Zhou">PMID:20616231</ref>
+The Fab region of the antibody is where antigen recognition occurs upon binding (Figure 1). On each arm is one heavy ('''{{Font color|violet|A}}'''/<b><span class="text-blue">B</span></b>) and one light (<b><span class="text-purple">A</span></b>/<b><span class="text-cyan">B</span></b>) chain, both containing domains identical to their respective counterparts. Repeats of β-sandwiches form the [https://en.wikipedia.org/wiki/Antibody constant and variable domains] within the Fab region. Antigen recognition occurs at the variable domain while the constant domain connects it to the rest of the IgM complex. Because the Fab region of IgM is poorly resolved, a structural analysis of an HIV neutralizing antibody called VCR01 was performed to approximate where an antigen would bind to at the  <scene name='95/952714/Variable_region/1'>variable region</scene>. <ref name="Zhou">PMID:20616231</ref>
 The IgM-BCR contains areas referred to as [https://en.wikipedia.org/wiki/Complementarity-determining_region complementary-determining regions](CDRs), which are where the antigen makes <scene name='95/952713/Antigen_antibody_contact/2'>contact</scene>  with the antibody on the Fab domain. Figure 2 depicts this as a surface representation given that the specific residues within the antigen-binding motif are unknown.
-Due to the poor resolution of the Fab region, specific side chain interactions between the heavy ('''{{Font color|violet|A}}'''/<b><span class="text-blue">B</span></b>) and light (<b><span class="text-purple">A</span></b>/<b><span class="text-cyan">B</span></b>) chains have not been determined. It is estimated that each β-sandwich contains one disulfide bridge with additional hydrogen bonds. The <scene name='95/952713/Heavy-light_chain_interface/2'>heavy-light chain interface</scene> shows how the four heavy and light chain β-sandwiches fit together. The Fab region heavy chains attach to the Fc region heavy chains, before continuing down into the intracellular domain to interact with the <b><span class="text-brown">Igα</span></b>/<b><span class="text-orange">Igβ</span></b> subunits. The light chains (<b><span class="text-purple">A</span></b>/<b><span class="text-cyan">B</span></b>) however are only connected to the heavy chains ('''{{Font color|violet|A}}'''/<b><span class="text-blue">B</span></b>) within the Fab region, thus have no contact with the <b><span class="text-brown">Igα</span></b>/<b><span class="text-orange">Igβ</span></b> heterodimer.
+Due to the poor resolution of the Fab region, specific side chain interactions between the heavy ('''{{Font color|violet|A}}'''/<b><span class="text-blue">B</span></b>) and light (<b><span class="text-purple">A</span></b>/<b><span class="text-cyan">B</span></b>) chains have not been determined. Based on the general structure of an [https://en.wikipedia.org/wiki/Antibody antibody] it is estimated that each β-sandwich contains one disulfide bridge with additional hydrogen bonds. The <scene name='95/952713/Heavy-light_chain_interface/2'>heavy-light chain interface</scene> shows how the four heavy and light chain β-sandwiches fit together. The Fab region heavy chains attach to the Fc region heavy chains, before continuing down into the intracellular domain to interact with the <b><span class="text-brown">Igα</span></b>/<b><span class="text-orange">Igβ</span></b> subunits. The light chains (<b><span class="text-purple">A</span></b>/<b><span class="text-cyan">B</span></b>) however are only connected to the heavy chains ('''{{Font color|violet|A}}'''/<b><span class="text-blue">B</span></b>) within the Fab region, thus have no contact with the <b><span class="text-brown">Igα</span></b>/<b><span class="text-orange">Igβ</span></b> heterodimer.
 [[Image:IgM_Surface2.png|400 px|left|thumb|'''Figure 3. Surface Representation of IgM Antibody Binding Pocket.''' On one arm of the IgM antibody, the antigen makes contact with light chain A at the L1 and L3 complementary-determining regions. Furthermore, it makes contact with heavy chain A at the H1, H2, and H3 complementary-determining regions. The location of the complementary-determining regions were approximated using the structure of the VCR01 variable region and were visualized using PyMOL.]]