Alpha crystallin: Difference between revisions

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== Function ==

Alpha crystallin is known to be one of the primary structural proteins of the eye's lens, specifically crystallin types alpha (α), beta (β), and gamma (γ). While all types have essential roles in the eye, alpha-crystallin and its subunits make up 40% of the lens's protein composition <ref> DOI: 10.1016/j.preteyeres.2006.10.003 </ref>. These crystallin proteins create stability in the lens and have the ability to impact an individual's vision because they provide lens transparency. In order to retain their eye's transparency in the absence of protein turnover, or the replacing and reproduction of proteins within a cell as the proteins become broken down, the protein must retain some form of longevity. Its longevity is generally assumed to be correlated with the long-term retention of its <scene name='88/881544/Native_structure/1'>native structure</scene>. Its ability to maintain the structure for a prolonged period of time is related to the N-terminal residue as this terminal is correlated with protein life. Even though the N-terminal does impact protein longevity, it does not determine a protein's half-life completely. In alpha-crystallin, the N-terminus contains approximately 60 residues, some of which include isoleucine and alanine <ref> DOI: 10.1016/j.pbiomolbio.2003.11.012 </ref>.

'''Alpha crystallin''' is known to be one of the primary structural proteins of the eye's lens, specifically crystallin types alpha (α), beta (β), and gamma (γ). While all types have essential roles in the eye, alpha-crystallin and its subunits make up 40% of the lens's protein composition <ref> DOI: 10.1016/j.preteyeres.2006.10.003 </ref>. These crystallin proteins create stability in the lens and have the ability to impact an individual's vision because they provide lens transparency. In order to retain their eye's transparency in the absence of protein turnover, or the replacing and reproduction of proteins within a cell as the proteins become broken down, the protein must retain some form of longevity. Its longevity is generally assumed to be correlated with the long-term retention of its <scene name='88/881544/Native_structure/1'>native structure</scene>. Its ability to maintain the structure for a prolonged period of time is related to the N-terminal residue as this terminal is correlated with protein life. Even though the N-terminal does impact protein longevity, it does not determine a protein's half-life completely. In alpha-crystallin, the N-terminus contains approximately 60 residues, some of which include isoleucine and alanine <ref> DOI: 10.1016/j.pbiomolbio.2003.11.012 </ref>.

This means that the half-life of an alpha-crystallin protein, based on the N-terminal residues' contents, may be about 20 hours <ref> DOI: 10.1126/science.3018930 </ref>. Its native structure can remain intact due to the efficient capture and refolding process of non-native proteins by the chaperones and the thermodynamic stability that the proteins have. Alpha-crystallins also provide vision clarity by regulating a proper refractive index within the eye. The lens contains a very high concentration of lens crystallins, primarily alpha-crystallin, and they remain densely packed within the space. This allows the lens to maintain a consistent refractive index over various distances, regardless of the light wavelength's location. They also have a particular arrangement of epithelial cells and fiber cells that lack organelles in their nucleases to reduce the blockage of light transmission to the eye <ref> DOI: 10.1016/j.pbiomolbio.2003.11.012 </ref>.

Along with the contents and structure of the lens itself, the alpha-crystallin maintains the eye's clarity by acting as chaperone-like proteins in order to prevent aberrant, or standard deviating, protein interactions. The chaperone capabilities of these proteins also allow the prevention of non-native proteins becoming insoluble under stressful conditions like chemical reductions, oxidations, or elevation of temperatures. The combined abilities of the chaperone-like alpha-crystallin means that they can aid in the prevention of the formation of large, dense, light scattering masses. For example, one of the effects of old age is cataract formation, and alpha-crystallin is the known culprit for this development. As alpha-crystallin is depleted within the eye, its defensive efforts go with it, which allows these masses to take form. The alpha-crystallin within the eye is the primary protectant against the age-induced deterioration of the lens. It allows the effects of aging to be reduced for significant periods of time.

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Both subunits are polydisperse, oligomeric proteins that are made of flexible monomers with large surface areas. This means that they are very low molecular weight polymers made of a small number of repeat units ranging in various sizes. Based on their surrounding environment, their oligomeric properties will vary. Due to their oligomeric properties, each of these subunits is able to associate and form about 40 chain-long, large complexes in the shape of a sphere called oligomeric complexes. These complexes form when the monomers dimerize, causing the amino region and carboxyl regions of the alpha-crystallin to interact with residues from other corresponding regions of their neighboring subunits <ref> DOI: 10.3390/biology9040085 </ref>. These spheres are so large and oppositely charged that they repel and distribute themselves across the lens cells. When combined to create alpha-crystallin, the proteins exist as globular aggregates whose quaternary structure is believed to behave as a protein micelle. However, high-resolution data about the quaternary and tertiary structure of alpha-crystallin is unavailable, which is likely due to the polydisperse nature of alpha-crystallin <ref> DOI: 10.1016/j.exer.2008.07.007 </ref>. After 50 years of extensive study, the three-dimensional structure remains unknown because the protein is too large for NMR measurements and has yet to be obtained for X-ray studies.

In humans, both of these crystalline forms are coded for on different chromosomes. While they may be coded differently, they possess about 55% sequence homology between themselves. This means that they are structurally similar due to the evolutionary pathway and ancestral history that they both underwent. Despite their similar makeups, they do have unique features about them. For example, alpha-B crystallin is stress-inducible while alpha-A crystallin is not. This implies that alpha-B crystallin has a distinct role in the eye's lens.

Alpha-A crystallin is made of 173 amino acids arranged in <scene name='88/881544/Beta_sheet/1'>a beta sheet pattern</scene>. The molecular mass of the alpha-A subunit is 19.8 kDa, and the homooligomer weighs 660 kDa. On the other hand, Alpha-B crystallin has 165 amino acids arranged in seven beta-sheets, has a molecular mass of 20 kDa, and its homooligomer weight is 620 kDa. Together, the alpha-crystallin protein has <scene name='88/881544/Zinc_and_zinc_binding_sites/3'>four Zinc binding sites</scene>, all of which are in the same position as the four metal-binding sites. They also contain <scene name='88/881544/Glycerol_binding_site/1'>four glycerol binding sites</scene>. Within the crystallin is two tryptophan residues, Trp9 and Trp60, both of which can be found in the alpha-B crystallin subunit <ref> DOI: 10.1110/ps.8.12.2761 </ref>.

Alpha-A crystallin is made of 173 amino acids arranged in <scene name='88/881544/Beta_sheet/1'>a beta sheet pattern</scene>. The molecular mass of the alpha-A subunit is 19.8 kDa, and the homooligomer weighs 660 kDa. On the other hand, Alpha-B crystallin has 165 amino acids arranged in seven beta-sheets, has a molecular mass of 20 kDa, and its homooligomer weight is 620 kDa. Together, the alpha-crystallin protein has <scene name='88/881544/Zinc_and_zinc_binding_sites/5'>four Zinc binding sites</scene>, all of which are in the same position as the four metal-binding sites. They also contain <scene name='88/881544/Glycerol_binding_site/1'>four glycerol binding sites</scene>. Within the crystallin is two tryptophan residues, Trp9 and Trp60, both of which can be found in the alpha-B crystallin subunit <ref> DOI: 10.1110/ps.8.12.2761 </ref>.

== Evolutionary Development ==

Alpha crystallin: Difference between revisions

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-<Structure load='3L1E' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
+<Structure load='3L1E' size='350' frame='true' align='right' caption='Bovine alpha-cystallin A chain residues 59-163 complex with Zn+2 (grey) and glycerol (PDB code [[3l1e]])' scene='Insert optional scene name here' />
 == Function ==
-Alpha crystallin is known to be one of the primary structural proteins of the eye's lens, specifically crystallin types alpha (α), beta (β), and gamma (γ). While all types have essential roles in the eye, alpha-crystallin and its subunits make up 40% of the lens's protein composition <ref> DOI: 10.1016/j.preteyeres.2006.10.003 </ref>. These crystallin proteins create stability in the lens and have the ability to impact an individual's vision because they provide lens transparency. In order to retain their eye's transparency in the absence of protein turnover, or the replacing and reproduction of proteins within a cell as the proteins become broken down, the protein must retain some form of longevity. Its longevity is generally assumed to be correlated with the long-term retention of its <scene name='88/881544/Native_structure/1'>native structure</scene>. Its ability to maintain the structure for a prolonged period of time is related to the N-terminal residue as this terminal is correlated with protein life. Even though the N-terminal does impact protein longevity, it does not determine a protein's half-life completely. In alpha-crystallin, the N-terminus contains approximately 60 residues, some of which include isoleucine and alanine <ref> DOI: 10.1016/j.pbiomolbio.2003.11.012 </ref>.
+'''Alpha crystallin''' is known to be one of the primary structural proteins of the eye's lens, specifically crystallin types alpha (α), beta (β), and gamma (γ). While all types have essential roles in the eye, alpha-crystallin and its subunits make up 40% of the lens's protein composition <ref> DOI: 10.1016/j.preteyeres.2006.10.003 </ref>. These crystallin proteins create stability in the lens and have the ability to impact an individual's vision because they provide lens transparency. In order to retain their eye's transparency in the absence of protein turnover, or the replacing and reproduction of proteins within a cell as the proteins become broken down, the protein must retain some form of longevity. Its longevity is generally assumed to be correlated with the long-term retention of its <scene name='88/881544/Native_structure/1'>native structure</scene>. Its ability to maintain the structure for a prolonged period of time is related to the N-terminal residue as this terminal is correlated with protein life. Even though the N-terminal does impact protein longevity, it does not determine a protein's half-life completely. In alpha-crystallin, the N-terminus contains approximately 60 residues, some of which include isoleucine and alanine <ref> DOI: 10.1016/j.pbiomolbio.2003.11.012 </ref>.
 This means that the half-life of an alpha-crystallin protein, based on the N-terminal residues' contents, may be about 20 hours <ref> DOI: 10.1126/science.3018930 </ref>. Its native structure can remain intact due to the efficient capture and refolding process of non-native proteins by the chaperones and the thermodynamic stability that the proteins have. Alpha-crystallins also provide vision clarity by regulating a proper refractive index within the eye. The lens contains a very high concentration of lens crystallins, primarily alpha-crystallin, and they remain densely packed within the space. This allows the lens to maintain a consistent refractive index over various distances, regardless of the light wavelength's location. They also have a particular arrangement of epithelial cells and fiber cells that lack organelles in their nucleases to reduce the blockage of light transmission to the eye <ref> DOI: 10.1016/j.pbiomolbio.2003.11.012 </ref>.
 Along with the contents and structure of the lens itself, the alpha-crystallin maintains the eye's clarity by acting as chaperone-like proteins in order to prevent aberrant, or standard deviating, protein interactions. The chaperone capabilities of these proteins also allow the prevention of non-native proteins becoming insoluble under stressful conditions like chemical reductions, oxidations, or elevation of temperatures. The combined abilities of the chaperone-like alpha-crystallin means that they can aid in the prevention of the formation of large, dense, light scattering masses. For example, one of the effects of old age is cataract formation, and alpha-crystallin is the known culprit for this development. As alpha-crystallin is depleted within the eye, its defensive efforts go with it, which allows these masses to take form. The alpha-crystallin within the eye is the primary protectant against the age-induced deterioration of the lens. It allows the effects of aging to be reduced for significant periods of time.
@@ Line 13: / Line 13: @@
 Both subunits are polydisperse, oligomeric proteins that are made of flexible monomers with large surface areas. This means that they are very low molecular weight polymers made of a small number of repeat units ranging in various sizes. Based on their surrounding environment, their oligomeric properties will vary. Due to their oligomeric properties, each of these subunits is able to associate and form about 40 chain-long, large complexes in the shape of a sphere called oligomeric complexes. These complexes form when the monomers dimerize, causing the amino region and carboxyl regions of the alpha-crystallin to interact with residues from other corresponding regions of their neighboring subunits <ref> DOI: 10.3390/biology9040085 </ref>. These spheres are so large and oppositely charged that they repel and distribute themselves across the lens cells. When combined to create alpha-crystallin, the proteins exist as globular aggregates whose quaternary structure is believed to behave as a protein micelle. However, high-resolution data about the quaternary and tertiary structure of alpha-crystallin is unavailable, which is likely due to the polydisperse nature of alpha-crystallin <ref> DOI: 10.1016/j.exer.2008.07.007 </ref>. After 50 years of extensive study, the three-dimensional structure remains unknown because the protein is too large for NMR measurements and has yet to be obtained for X-ray studies.
 In humans, both of these crystalline forms are coded for on different chromosomes. While they may be coded differently, they possess about 55% sequence homology between themselves. This means that they are structurally similar due to the evolutionary pathway and ancestral history that they both underwent. Despite their similar makeups, they do have unique features about them. For example, alpha-B crystallin is stress-inducible while alpha-A crystallin is not. This implies that alpha-B crystallin has a distinct role in the eye's lens.
-Alpha-A crystallin is made of 173 amino acids arranged in <scene name='88/881544/Beta_sheet/1'>a beta sheet pattern</scene>. The molecular mass of the alpha-A subunit is 19.8 kDa, and the homooligomer weighs 660 kDa. On the other hand, Alpha-B crystallin has 165 amino acids arranged in seven beta-sheets, has a molecular mass of 20 kDa, and its homooligomer weight is 620 kDa. Together, the alpha-crystallin protein has <scene name='88/881544/Zinc_and_zinc_binding_sites/3'>four Zinc binding sites</scene>, all of which are in the same position as the four metal-binding sites. They also contain <scene name='88/881544/Glycerol_binding_site/1'>four glycerol binding sites</scene>. Within the crystallin is two tryptophan residues, Trp9 and Trp60, both of which can be found in the alpha-B crystallin subunit  <ref> DOI: 10.1110/ps.8.12.2761 </ref>.
+Alpha-A crystallin is made of 173 amino acids arranged in <scene name='88/881544/Beta_sheet/1'>a beta sheet pattern</scene>. The molecular mass of the alpha-A subunit is 19.8 kDa, and the homooligomer weighs 660 kDa. On the other hand, Alpha-B crystallin has 165 amino acids arranged in seven beta-sheets, has a molecular mass of 20 kDa, and its homooligomer weight is 620 kDa. Together, the alpha-crystallin protein has <scene name='88/881544/Zinc_and_zinc_binding_sites/5'>four Zinc binding sites</scene>, all of which are in the same position as the four metal-binding sites. They also contain <scene name='88/881544/Glycerol_binding_site/1'>four glycerol binding sites</scene>. Within the crystallin is two tryptophan residues, Trp9 and Trp60, both of which can be found in the alpha-B crystallin subunit  <ref> DOI: 10.1110/ps.8.12.2761 </ref>.
 == Evolutionary Development ==