gamma-crystallins are associated with cataract in both human and animal models. gS-crystallin is the major bg-crystallin in the adult human lens and has also been found to be induced in retinal pigment epithelium in models of macular degeneration. The gene for gS has been ablated in mouse, leading to disruption of normal fiber cell maturation. This is associated with abnormalities in key components of the architecture of the fiber cells, suggesting a functional role for crystallins in maintaining cell structure both in lens and elsewhere in the eye. Experiments are underway to measure directly the possible role of gS in assembly of key cellular structures. Examination of older knockout mice is also providing evidence for defects in other parts of the eye that may provide a model for aging. Collaborative studies using NMR structure analysis are shedding light on the processes of unfolding and amyloid formation in the mouse gS mutant Opj. This has wider significance for understanding how normally folded proteins can unfold and adopt other structures that can have serious consequences for cellular function.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000255-22
Application #
8149136
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
22
Fiscal Year
2010
Total Cost
$508,827
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
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 (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
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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