Abstract

Tissues of the eye depend on families of specialized proteins. The major families of the lens are called crystallins. We have shown that in humans and other species crystallins have arisen by gene recruitement of proteins with functions that predate their role in lens. In some species these include enzymes recruited to serve an additionl structural role in lens transparency. Other familes are ubiquitous in vertebrates and seem to be derived from proteins with roles in stress and cell morphology.Currently we are actively examining the origins and functions of the ancient beta(b) and gamma (g) crystallins. Non-lens relatives with stress and cancer related functions have been identified. We have also shown that gS crystallin and bA2 crystallin have non-lens expression possibly relecting a non-lens function. We have found that gS is the locus of the Opj cataract in mouse and have evidence for loss of function in control of fiber cell structure. Recombinant wild type and mutant proteins for gS and human gD have been produced for functional studies. We have also found that two other novel genes overlap the gS gene in human and mouse. - Crystallins, function, evolution, gene recruitement

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000255-11
Application #
6290119
Study Section
Special Emphasis Panel (MSF)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Aravind, Penmatsa; Wistow, Graeme; Sharma, Yogendra et al. (2008) Exploring the limits of sequence and structure in a variant betagamma-crystallin domain of the protein absent in melanoma-1 (AIM1). J Mol Biol 381:509-18
Nag, Nabanita; Peterson, Katherine; Wyatt, Keith et al. (2007) Endogenous retroviral insertion in Cryge in the mouse No3 cataract mutant. Genomics 89:512-20
Purkiss, Andrew G; Bateman, Orval A; Wyatt, Keith et al. (2007) Biophysical properties of gammaC-crystallin in human and mouse eye lens: the role of molecular dipoles. J Mol Biol 372:205-22
Smith, Amber A; Wyatt, Keith; Vacha, Jennifer et al. (2006) Gene duplication and separation of functions in alphaB-crystallin from zebrafish (Danio rerio). FEBS J 273:481-90
Vihtelic, Thomas S; Fadool, James M; Gao, James et al. (2005) Expressed sequence tag analysis of zebrafish eye tissues for NEIBank. Mol Vis 11:1083-100
Wu, Zhengrong; Delaglio, Frank; Wyatt, Keith et al. (2005) Solution structure of (gamma)S-crystallin by molecular fragment replacement NMR. Protein Sci 14:3101-14
Fan, Jianguo; Fariss, Robert N; Purkiss, Andrew G et al. (2005) Specific interaction between lens MIP/Aquaporin-0 and two members of the gamma-crystallin family. Mol Vis 11:76-87
Wistow, Graeme; Wyatt, Keith; David, Larry et al. (2005) gammaN-crystallin and the evolution of the betagamma-crystallin superfamily in vertebrates. FEBS J 272:2276-91
Evans, P; Wyatt, K; Wistow, G J et al. (2004) The P23T cataract mutation causes loss of solubility of folded gammaD-crystallin. J Mol Biol 343:435-44
Wallace, B A; Wien, Frank; Miles, Andrew J et al. (2004) Biomedical applications of synchrotron radiation circular dichroism spectroscopy: identification of mutant proteins associated with disease and development of a reference database for fold motifs. Faraday Discuss 126:237-43; discussion 245-54

Showing the most recent 10 out of 17 publications