The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Joseph Horwitz - One of the best experts on this subject based on the ideXlab platform.
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Altered Chaperone-like Activity of α-Crystallins Promotes Cataractogenesis
Journal of Biological Chemistry, 2010Co-Authors: Catherine Cheng, Linlin Ding, Joseph Horwitz, Qingling Huang, Xiaohua GongAbstract:Abstract Despite the enormous number of studies demonstrating changes in the chaperone-like activity of α-Crystallins in vitro, little is known about how these changes influence life-long lens transparency in vivo. Using the γB-Crystallin I4F mutant protein as a target for αA-Crystallins, we examined how cataract phenotypes are modulated by interactions between α-Crystallins with altered chaperone-like activities and γB-I4F proteins in vivo. Double heterozygous α-Crystallin knock-out αA(+/−) αB(+/−) mice with a decreased amount of α-Crystallins were used to simulate reduced total α-Crystallin chaperone-like activity in vivo. We found that triple heterozygous αA(+/−) αB(+/−) γB(I4F/+) mice developed more severe whole cataracts than heterozygous γB(I4F/+) mice. Thus, total chaperone-like activity of α-Crystallins is important for maintaining lens transparency. We further tested whether mutant αA-Crystallin Y118D proteins with increased chaperone-like activity influenced the whole cataract caused by the γB-I4F mutation. Unexpectedly, compound αA(Y118D/+) γB(I4F/+) mutant lenses displayed severe nuclear cataracts, whereas the lens cortex remained unaffected. Thus, the synergistic effect of αA-Y118D and γB-I4F mutant proteins is detrimental to the transparency only in the lens core. α-Crystallins with different chaperone-like activities are likely required in the lens cortex and nucleus for maintaining transparency.
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Alpha-Crystallin.
Experimental Eye Research, 2003Co-Authors: Joseph HorwitzAbstract:Alpha A and alpha B-Crystallins are a major protein component of the mammalian eye lens. Being a member of the small heat-shock protein family they possess chaperone-like function. The alpha-Crystallins and especially alpha B is also found outside the lens having an extensive tissue distribution. Alpha B-Crystallin is found to be over-expressed in many neurological diseases, and mutations in alpha A or B-Crystallin can cause cataract and myopathy. This review deals with some of the unique properties of the alpha-Crystallins emphasizing especially what we don't know about its function and structure.
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Ω-Crystallin of the Scallop Lens A DIMERIC ALDEHYDE DEHYDROGENASE CLASS 1/2 ENZYME-Crystallin
The Journal of biological chemistry, 2000Co-Authors: Joram Piatigorsky, Linlin Ding, Joseph Horwitz, Zbynek Kozmik, Eleonora Carosa, W. Gerald Robison, Peter J. Steinbach, Ernst R. TammAbstract:Abstract While many of the diverse Crystallins of the transparent lens of vertebrates are related or identical to metabolic enzymes, much less is known about the lens Crystallins of invertebrates. Here we investigate the complex eye of scallops. Electron microscopic inspection revealed that the anterior, single layered corneal epithelium overlying the cellular lens contains a regular array of microvilli that we propose might contribute to its optical properties. The sole Crystallin of the scallop eye lens was found to be homologous to Ω-Crystallin, a minor Crystallin in cephalopods related to aldehyde dehydrogenase (ALDH) class 1/2. Scallop Ω-Crystallin (officially designated ALDH1A9) is 55–56% identical to its cephalopod homologues, while it is 67 and 64% identical to human ALDH 2 and 1, respectively, and 61% identical to retinaldehyde dehydrogenase/η-Crystallin of elephant shrews. Like other enzyme-Crystallins, scallop Ω-Crystallin appears to be present in low amounts in non-ocular tissues. Within the scallop eye, immunofluorescence tests indicated that Ω-Crystallin expression is confined to the lens and cornea. Although it has conserved the critical residues required for activity in other ALDHs and appears by homology modeling to have a structure very similar to human ALDH2, scallop Ω-Crystallin was enzymatically inactive with diverse substrates and did not bind NAD or NADP. In contrast to mammalian ALDH1 and -2 and other cephalopod Ω-Crystallins, which are tetrameric proteins, scallop Ω-Crystallin is a dimeric protein. Thus, ALDH is the most diverse lens enzyme-Crystallin identified so far, having been used as a lens Crystallin in at least two classes of molluscs as well as elephant shrews.
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the function of alpha Crystallin in vision
Seminars in Cell & Developmental Biology, 2000Co-Authors: Joseph HorwitzAbstract:Abstract The alpha-Crystallins account for approximately one-third of the total soluble protein in the lens, contributing to its refractive power. In addition, alpha-Crystallin also has a chaperone-like function and thus can bind unfolding lens proteins. Alpha B-Crystallin is also found outside the lens, having an extensive tissue distribution. It is over-expressed in response to stresses of all kinds, where it is thought to serve a general protective function. Recently, it has been shown in humans that naturally occurring point mutations in the alpha-Crystallins result in a deficit in chaperone-like function, and cause cataracts as well as a desmin-related myopathy. This review summarizes much of the past and current knowledge concerning the structure and functions of alpha-Crystallin.
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alpha Crystallin can function as a molecular chaperone
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Joseph HorwitzAbstract:Abstract The alpha-Crystallins (alpha A and alpha B) are major lens structural proteins of the vertebrate eye that are related to the small heat shock protein family. In addition, Crystallins (especially alpha B) are found in many cells and organs outside the lens, and alpha B is overexpressed in several neurological disorders and in cell lines under stress conditions. Here I show that alpha-Crystallin can function as a molecular chaperone. Stoichiometric amounts of alpha A and alpha B suppress thermally induced aggregation of various enzymes. In particular, alpha-Crystallin is very efficient in suppressing the thermally induced aggregation of beta- and gamma-Crystallins, the two other major mammalian structural lens proteins. alpha-Crystallin was also effective in preventing aggregation and in refolding guanidine hydrochloride-denatured gamma-Crystallin, as judged by circular dichroism spectroscopy. My results thus indicate that alpha-Crystallin refracts light and protects proteins from aggregation in the transparent eye lens and that in nonlens cells alpha-Crystallin may have other functions in addition to its capacity to suppress aggregation of proteins.
Joram Piatigorsky - One of the best experts on this subject based on the ideXlab platform.
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Evolution of Mollusc Lens Crystallins: Glutathione S-transferase/S-Crystallins and Aldehyde Dehydrogenase/Ω-Crystallins*
American Malacological Bulletin, 2008Co-Authors: Joram PiatigorskyAbstract:Abstract: Diverse Crystallins (abundant water-soluble proteins) are responsible for the optical properties of transparent cellular eye lenses and are multifunctional proteins that have been recruited from stress proteins and enzymes by enhanced lens expression. The major (S-Crystallins) and minor (Ω-Crystallin) cephalopod Crystallins were recruited from glutathione S-transferase (GST) and aldehyde dehydrogenase (ALDH), respectively. S-Crystallins underwent multiple gene duplications while Ω-Crystallin appears to be encoded in a single-copy gene. Except for one S-Crystallin (considered a “molecular fossil”), S-Crystallins lack enzyme activity due to mutation and insertion of a variable central peptide by exon shuffling. The Ω-Crystallin is the sole Crystallin in scallops. Scallop Ω-Crystallin does not bind the co-factor NAD+/NADH, lacks enzyme activity, and is a tetramer but migrates as a dimer by gel filtration, suggesting structural adaptations for Crystallin function. Similar transcription factors (Pax6...
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Ω-Crystallin of the Scallop Lens A DIMERIC ALDEHYDE DEHYDROGENASE CLASS 1/2 ENZYME-Crystallin
The Journal of biological chemistry, 2000Co-Authors: Joram Piatigorsky, Linlin Ding, Joseph Horwitz, Zbynek Kozmik, Eleonora Carosa, W. Gerald Robison, Peter J. Steinbach, Ernst R. TammAbstract:Abstract While many of the diverse Crystallins of the transparent lens of vertebrates are related or identical to metabolic enzymes, much less is known about the lens Crystallins of invertebrates. Here we investigate the complex eye of scallops. Electron microscopic inspection revealed that the anterior, single layered corneal epithelium overlying the cellular lens contains a regular array of microvilli that we propose might contribute to its optical properties. The sole Crystallin of the scallop eye lens was found to be homologous to Ω-Crystallin, a minor Crystallin in cephalopods related to aldehyde dehydrogenase (ALDH) class 1/2. Scallop Ω-Crystallin (officially designated ALDH1A9) is 55–56% identical to its cephalopod homologues, while it is 67 and 64% identical to human ALDH 2 and 1, respectively, and 61% identical to retinaldehyde dehydrogenase/η-Crystallin of elephant shrews. Like other enzyme-Crystallins, scallop Ω-Crystallin appears to be present in low amounts in non-ocular tissues. Within the scallop eye, immunofluorescence tests indicated that Ω-Crystallin expression is confined to the lens and cornea. Although it has conserved the critical residues required for activity in other ALDHs and appears by homology modeling to have a structure very similar to human ALDH2, scallop Ω-Crystallin was enzymatically inactive with diverse substrates and did not bind NAD or NADP. In contrast to mammalian ALDH1 and -2 and other cephalopod Ω-Crystallins, which are tetrameric proteins, scallop Ω-Crystallin is a dimeric protein. Thus, ALDH is the most diverse lens enzyme-Crystallin identified so far, having been used as a lens Crystallin in at least two classes of molluscs as well as elephant shrews.
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Review: A case for corneal Crystallins.
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2000Co-Authors: Joram PiatigorskyAbstract:It is established that the diverse, multifunctional Crystallins are responsible for the optical properties of the cellular, transparent lens of the complex eyes of vertebrates and invertebrates. Lens Crystallins often differ among species and may be enzymes or stress proteins. I present here the idea that abundant water-soluble enzymes and other proteins may also be used for cellular transparency in the epithelial cells and, possibly, stromal keratocytes of the cornea. Aldehyde dehydrogenases and transketolase are among the putative "corneal Crystallins" in mammals, and gelsolin may be a corneal Crystallin in the zebrafish. In invertebrates, the glutathione S-transferase-related S-Crystallins of the lens appear to be used also as corneal Crystallins in the squid, and an aldehyde dehydrogenase-related protein is the Crystallin in the lens and, possibly, cornea of the scallop. The use of abundant, taxon-specific water-soluble proteins as Crystallins for cellular transparency in the cornea would provide a new conceptual link between this tissue and the lens.
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Lens Crystallins of Invertebrates
European journal of biochemistry, 1996Co-Authors: Stanislav I. Tomarev, Joram PiatigorskyAbstract:The major proteins (Crystallins) of the transparent, refractive eye lens of vertebrates are a surprisingly diverse group of multifunctional proteins. A number of lens Crystallins display taxon-specificity. In general, vertebrate Crystallins have been recruited from stress-protective proteins (i.e. the small heat-shock proteins) and a number of metabolic enzymes by a gene-sharing mechanism. Despite the existence of refractive lenses in the complex and compound eyes of many invertebrates, relatively little is known about their Crystallins. Here we review for the first time the state of knowledge of invertebrate Crystallins. The major cephalopod (squid, octopus, and cuttlefish) Crystallins (S-Crystallins) have, like vertebrate Crystallins, been recruited from a stress protective metabolic enzyme, glutathione S-transferase. The presence of overlapping AP-1 and antioxidant responsive-like sequences that appear functional in transfected vertebrate cells suggests that the recruitment of glutathione S-transferase to S-Crystallins involved response to oxidative stress. Cephalopods also have at least two taxon-specific Crystallins: Ω-Crystallin, related to aldehyde dehydrogenase, and O-Crystallin, related to a superfamily of lipid-binding proteins. L-Crystallin (probably identical to Ω-Crystallin) is the major protein of the lens of the squid photophore, a specialized structure for emitting light. The use of L/Ω-Crystallin in the ectodermal lens of the eye and the mesodermal lens of the photophore of the squid contrasts with the recruitment of different Crystallins in the ectodermal lenses of the eye and photophore of fish. S- and Ω-Crystallins appear to be lens-specific (some S-Crystallins are also expressed in cornea) and, except for one S-Crystallin polypeptide (SL11/Lops4; possibly a molecular fossil), lack enzymatic activity. The S-Crystallins (except SLll/Lops4) contain a variable peptide that has been inserted by exon shuffling. The only other invertebrate Crystallins that have been examined are in one marine gastropod (Aplysia, a sea hare), in jellyfish and in the compound eyes of some arthropods; all are different and novel proteins. DrosoCrystallin is one of three calcium binding taxon-specific Crystallins found selectively in the acellular corneal lens of Drosophila, while antigen 3G6 is a highly conserved protein present in the ommatidial Crystallin cone and central nervous system of numerous arthropods. Cubomedusan jellyfish have three novel Crystallin families (the J-Crystallins); the J1-Crystallins are encoded in three very similar intronless genes with markedly different 5′ flanking sequences despite their almost identical encoded proteins and high lens expression. The numerous refractive structures that have evolved in the eyes of invertebrates contrast markedly with the limited information on their protein composition, making this field as exciting as it is underdeveloped. The similar requirement of Pax-6 (and possibly other common transcription factors) for eye development as well as the diversity, taxon-specificity and recruitment of stress-protective enzymes as Crystallins suggest that borrowing multifunctional proteins for refraction by a gene sharing strategy may have occurred in invertebrates as it did in vertebrates.
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alpha Crystallin small heat shock protein has autokinase activity
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Marc Kantorow, Joram PiatigorskyAbstract:The alpha-Crystallins (alpha A and alpha B) are major water-soluble proteins of the transparent eye lens that are expressed in a variety of tissues and can function as molecular chaperones. alpha B-Crystallin is also a small heat shock protein associated with numerous degenerative diseases and abnormal growth patterns. Previous experiments have shown that alpha A-and alpha B-Crystallin are phosphorylated on specific serine residues by a cAMP-dependent pathway. Here we provide evidence that either total bovine alpha-Crystallin or its isolated polypeptides can autophosphorylate serine by a cAMP-independent mechanism in the presence of Mg2+ and [gamma-32P]ATP; the autophosphorylated products isoelectrically focus with the authentic phosphorylated forms of the alpha-Crystallin polypeptides. Thus, the alpha A- and alpha B-Crystallin/small heat shock protein polypeptides are enzyme-Crystallins which may be involved in metabolic pathways important for the development, maintenance, or pathology of the lens and other tissues.
Marc Kantorow - One of the best experts on this subject based on the ideXlab platform.
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alpha Crystallin small heat shock protein has autokinase activity
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Marc Kantorow, Joram PiatigorskyAbstract:The alpha-Crystallins (alpha A and alpha B) are major water-soluble proteins of the transparent eye lens that are expressed in a variety of tissues and can function as molecular chaperones. alpha B-Crystallin is also a small heat shock protein associated with numerous degenerative diseases and abnormal growth patterns. Previous experiments have shown that alpha A-and alpha B-Crystallin are phosphorylated on specific serine residues by a cAMP-dependent pathway. Here we provide evidence that either total bovine alpha-Crystallin or its isolated polypeptides can autophosphorylate serine by a cAMP-independent mechanism in the presence of Mg2+ and [gamma-32P]ATP; the autophosphorylated products isoelectrically focus with the authentic phosphorylated forms of the alpha-Crystallin polypeptides. Thus, the alpha A- and alpha B-Crystallin/small heat shock protein polypeptides are enzyme-Crystallins which may be involved in metabolic pathways important for the development, maintenance, or pathology of the lens and other tissues.
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Alpha-Crystallin/small heat shock protein has autokinase activity.
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Marc Kantorow, Joram PiatigorskyAbstract:The alpha-Crystallins (alpha A and alpha B) are major water-soluble proteins of the transparent eye lens that are expressed in a variety of tissues and can function as molecular chaperones. alpha B-Crystallin is also a small heat shock protein associated with numerous degenerative diseases and abnormal growth patterns. Previous experiments have shown that alpha A-and alpha B-Crystallin are phosphorylated on specific serine residues by a cAMP-dependent pathway. Here we provide evidence that either total bovine alpha-Crystallin or its isolated polypeptides can autophosphorylate serine by a cAMP-independent mechanism in the presence of Mg2+ and [gamma-32P]ATP; the autophosphorylated products isoelectrically focus with the authentic phosphorylated forms of the alpha-Crystallin polypeptides. Thus, the alpha A- and alpha B-Crystallin/small heat shock protein polypeptides are enzyme-Crystallins which may be involved in metabolic pathways important for the development, maintenance, or pathology of the lens and other tissues.
Christine Slingsby - One of the best experts on this subject based on the ideXlab platform.
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Association of partially folded lens βB2-Crystallins with the α-Crystallin molecular chaperone
The Biochemical journal, 2008Co-Authors: Paul C. Evans, Christine Slingsby, Bonnie A. WallaceAbstract:Age-related cataract is a result of Crystallins, the predominant lens proteins, forming light-scattering aggregates. In the low protein turnover environment of the eye lens, the Crystallins are susceptible to modifications that can reduce stability, increasing the probability of unfolding and aggregation events occurring. It is hypothesized that the alpha-Crystallin molecular chaperone system recognizes and binds these proteins before they can form the light-scattering centres that result in cataract, thus maintaining the long-term transparency of the lens. In the present study, we investigated the unfolding and aggregation of (wild-type) human and calf betaB2-Crystallins and the formation of a complex between alpha-Crystallin and betaB2-Crystallins under destabilizing conditions. Human and calf betaB2-Crystallin unfold through a structurally similar pathway, but the increased stability of the C-terminal domain of human betaB2-Crystallin relative to calf betaB2-Crystallin results in the increased population of a partially folded intermediate during unfolding. This intermediate is aggregation-prone and prevents constructive refolding of human betaB2-Crystallin, while calf betaB2-Crystallin can refold with high efficiency. alpha-Crystallin can effectively chaperone both human and calf betaB2-Crystallins from thermal aggregation, although chaperone-bound betaB2-Crystallins are unable to refold once returned to native conditions. Ordered secondary structure is seen to increase in alpha-Crystallin with elevated temperatures up to 60 degrees C; structure is rapidly lost at temperatures of 70 degrees C and above. Our experimental results combined with previously reported observations of alpha-Crystallin quaternary structure have led us to propose a structural model of how activated alpha-Crystallin chaperones unfolded betaB2-Crystallin.
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Association of partially-folded lens {beta}B2-Crystallins with the {alpha}-Crystallin molecular chaperone
Biochemical Journal, 2007Co-Authors: Paul Evans, Christine Slingsby, Bonnie A. WallaceAbstract:Age-related cataract is a result of Crystallins, the predominant lens proteins, forming light scattering aggregates. In the low protein turnover environment of the eye lens, the Crystallins are susceptible to modifications that can reduce stability, increasing the probability of unfolding and aggregation events occurring. It is hypothesised that the α-Crystallin molecular chaperone system recognises and binds these proteins before they can form the light scattering centres that result in cataract, thus maintaining the long-term transparency of the lens. In this study we investigated the unfolding and aggregation of (wildtype) human and calf βB2-Crystallins, and the formation of a complex between α-Crystallin and βB2-Crystallins under destabilising conditions. Human and calf βB2-Crystallin unfold through a structurally similar pathway, but the increased stability of the C-terminal domain of human βB2-Crystallin relative to calf βB2-Crystallin results in the increased population of a partially folded intermediate during unfolding. This intermediate is aggregation prone, and prevents constructive refolding of human βB2-Crystallin, whilst calf βB2-Crystallin can refold with high efficiency. α-Crystallin can effectively chaperone both human and calf βB2-Crystallin from thermal aggregation, though chaperone-bound βB2-Crystallins are unable to refold once returned to native conditions. Ordered secondary structure is seen to increase in α-Crystallin with elevated temperatures up to 60°C; structure is rapidly lost at temperatures of 70°C and above. Our experimental data combined with previously reported observations of α-Crystallin quaternary structure have lead us to propose a structural model of how activated α-Crystallin chaperones unfolded βB2-Crystallin.
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in vivo heteromer formation expression of soluble βa4 Crystallin requires coexpression of a heteromeric partner
FEBS Journal, 2006Co-Authors: Laura Marinvinader, Christine Slingsby, Carla Onnekink, Siebe T Van Genesen, Nicolette H. LubsenAbstract:The β-Crystallins are a family of long-lived, abundant structural proteins that are coexpressed in the vertebrate lens. As β-Crystallins form heteromers, a process that involves transient exposure of hydrophobic interfaces, we have examined whether in vivoβ-Crystallin assembly is enhanced by protein chaperones, either small heat shock proteins, Hsp27 or αB-Crystallin, or Hsp70. We show here that βA4-Crystallin is abundantly expressed in HeLa cells, but rapidly degraded, irrespective of the presence of Hsp27, αB-Crystallin or Hsp70. Degradation is even enhanced by Hsp70. Coexpression of βA4-Crystallin with βB2-Crystallin yielded abundant soluble βA4–βB2-Crystallin heteromers; βB1-Crystallin was much less effective in solubilizing βA4-Crystallin. As βB2-Crystallin competed for βA4-Crystallin with Hsp70 and the proteasomal degradation pathway, βB2-Crystallin probably captures an unstable βA4-Crystallin intermediate. We suggest that the proper folding of βA4-Crystallin is not mediated by general chaperones but requires a heteromeric partner, which then also acts as a dedicated chaperone towards βA4-Crystallin.
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γN‐Crystallin and the evolution of the βγ‐Crystallin superfamily in vertebrates
The FEBS journal, 2005Co-Authors: Graeme Wistow, Christine Slingsby, Larry L. David, Stanislav I. Tomarev, O.a. Bateman, Keith Wyatt, Chun Gao, Steven L. Bernstein, Lorenzo Segovia, Thomas S. VihtelicAbstract:The β and γ Crystallins are evolutionarily related families of proteins that make up a large part of the refractive structure of the vertebrate eye lens. Each family has a distinctive gene structure that reflects a history of successive gene duplications. A survey of γ-Crystallins expressed in mammal, reptile, bird and fish species (particularly in the zebrafish, Danio rerio) has led to the discovery of γN-Crystallin, an evolutionary bridge between the β and γ families. In all species examined, γN-Crystallins have a hybrid gene structure, half β and half γ, and thus appear to be the ‘missing link’ between the β and γ Crystallin lineages. Overall, there are four major classes of γ-Crystallin: the terrestrial group (including mammalian γA–F); the aquatic group (the fish γM-Crystallins); the γS group; and the novel γN group. Like the evolutionarily ancient β-Crystallins (but unlike the terrestrial γA–F and aquatic γM groups), both the γS and γN Crystallins form distinct clades with members in fish, reptiles, birds and mammals. In rodents, γN is expressed in nuclear fibers of the lens and, perhaps hinting at an ancestral role for the γ-Crystallins, also in the retina. Although well conserved throughout vertebrate evolution, γN in primates has apparently undergone major changes and possible loss of functional expression.
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Sulfur in human Crystallins
Experimental eye research, 2004Co-Authors: Durga Srikanthan, O.a. Bateman, Andrew G. Purkiss, Christine SlingsbyAbstract:Abstract Molecular models of human γ-Crystallins and the ‘α-Crystallin domain’ of human αA-Crystallin have been built based on available related X-ray crystal structures. The accessibilities of the component cysteine, methionine and tryptophan side chains in the Crystallin models have been calculated. The reactivities of these cysteines, which are oxidised in cataract, are assessed based on their known modifications and within the context of their location within the 3D models.
Graeme Wistow - One of the best experts on this subject based on the ideXlab platform.
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The human Crystallin gene families.
Human genomics, 2012Co-Authors: Graeme WistowAbstract:Crystallins are the abundant, long-lived proteins of the eye lens. The major human Crystallins belong to two different superfamilies: the small heat-shock proteins (α-Crystallins) and the βγ-Crystallins. During evolution, other proteins have sometimes been recruited as Crystallins to modify the properties of the lens. In the developing human lens, the enzyme betaine-homocysteine methyltransferase serves such a role. Evolutionary modification has also resulted in loss of expression of some human Crystallin genes or of specific splice forms. Crystallin organization is essential for lens transparency and mutations; even minor changes to surface residues can cause cataract and loss of vision.
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γN‐Crystallin and the evolution of the βγ‐Crystallin superfamily in vertebrates
The FEBS journal, 2005Co-Authors: Graeme Wistow, Christine Slingsby, Larry L. David, Stanislav I. Tomarev, O.a. Bateman, Keith Wyatt, Chun Gao, Steven L. Bernstein, Lorenzo Segovia, Thomas S. VihtelicAbstract:The β and γ Crystallins are evolutionarily related families of proteins that make up a large part of the refractive structure of the vertebrate eye lens. Each family has a distinctive gene structure that reflects a history of successive gene duplications. A survey of γ-Crystallins expressed in mammal, reptile, bird and fish species (particularly in the zebrafish, Danio rerio) has led to the discovery of γN-Crystallin, an evolutionary bridge between the β and γ families. In all species examined, γN-Crystallins have a hybrid gene structure, half β and half γ, and thus appear to be the ‘missing link’ between the β and γ Crystallin lineages. Overall, there are four major classes of γ-Crystallin: the terrestrial group (including mammalian γA–F); the aquatic group (the fish γM-Crystallins); the γS group; and the novel γN group. Like the evolutionarily ancient β-Crystallins (but unlike the terrestrial γA–F and aquatic γM groups), both the γS and γN Crystallins form distinct clades with members in fish, reptiles, birds and mammals. In rodents, γN is expressed in nuclear fibers of the lens and, perhaps hinting at an ancestral role for the γ-Crystallins, also in the retina. Although well conserved throughout vertebrate evolution, γN in primates has apparently undergone major changes and possible loss of functional expression.