gamma-crystallins are associated with cataract in both human and animal models. To explore the functional characteristics of g-crystallins, proteins from fish and birds representing the extremes of the family in composition and behavior have been expressed. Using recombinant g-crystallins in several biophysical studies, we have shown that they have highly unusual solution properties that fit them for high protein concentration environments and shed light on how they unfold under stress. Studies on chicken gS-crystallin show how a single amino acid change in ancient ancestors of birds significantly affecetd the structure and stability of the protein. This protein also exhibits remarkable properties in solution that suggest it may be a model for a stage in the process of unfolding. This and other work is shedding light on the processes of unfolding and amyloid formation involving crystallins and the also the protective, chaperone role of a-crystallin. This has wider significance for understanding how normally folded proteins can unfold and adopt other structures that can have serious consequences for cellular function. Detailed NMR structure analysis has been used to determine the first structure of gM7-crystallin from zebrafish, representing an extreme member of the family in terms of composition and behavior. The structure is generally well-conserved but illustrates some specific changes resulting from replacement of key residues that show how those residues contribute to the tightly folded structure of human gamma-crystallins. Other studies

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000255-25
Application #
8737607
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
2013
Total Cost
$366,407
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Sagar, Vatsala; Chaturvedi, Sumit K; Schuck, Peter et al. (2017) Crystal Structure of Chicken ?S-Crystallin Reveals Lattice Contacts with Implications for Function in the Lens and the Evolution of the ??-Crystallins. Structure 25:1068-1078.e2
Chen, Yingwei; Sagar, Vatsala; Len, Hoay-Shuen et al. (2016) ?-Crystallins of the chicken lens: remnants of an ancient vertebrate gene family in birds. FEBS J 283:1516-30
Slingsby, Christine; Wistow, Graeme J (2014) Functions of crystallins in and out of lens: roles in elongated and post-mitotic cells. Prog Biophys Mol Biol 115:52-67
Wistow, Graeme J; Slingsby, Christine (2014) Editorial for special issue: crystallins of the eye. Prog Biophys Mol Biol 115:1-2
Chen, Yingwei; Zhao, Huaying; Schuck, Peter et al. (2014) Solution properties of ?-crystallins: compact structure and low frictional ratio are conserved properties of diverse ?-crystallins. Protein Sci 23:76-87
Zhao, Huaying; Chen, Yingwei; Rezabkova, Lenka et al. (2014) Solution properties of ?-crystallins: hydration of fish and mammal ?-crystallins. Protein Sci 23:88-99
Slingsby, Christine; Wistow, Graeme J; Clark, Alice R (2013) Evolution of crystallins for a role in the vertebrate eye lens. Protein Sci 22:367-80
Mahler, Bryon; Chen, Yingwei; Ford, Jason et al. (2013) Structure and dynamics of the fish eye lens protein, ?M7-crystallin. Biochemistry 52:3579-87
Wistow, Graeme (2012) The human crystallin gene families. Hum Genomics 6:26
Fan, Jianguo; Dong, Lijin; Mishra, Sanghamitra et al. (2012) A role for ?S-crystallin in the organization of actin and fiber cell maturation in the mouse lens. FEBS J 279:2892-904

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