DOMAIN INTERACTIONS IN CRYSTALLINS. G. Wright¹, B. Norledge¹, H. Driessen¹, C. Slingsby¹, R. Kroone², E. Mayr³, S. Trinkl³, A. Basak^{1, 1}Department of Crystallography, Birkbeck College, Malet St. London, UK. ²Department of Molecular Biology, University of Nijmegen, The Netherlands. ³Biophysics Institute, University of Regensburg, Germany

Transparency and refraction of eye lenses are dependent on the spatial organisation of the lens [[alpha]]-, [[beta]]- and [[gamma]]-crystallin proteins. Random aggregation and phase separation cause sharp discontinuities in the index of refraction leading to light scattering and cataract. The oligomeric [[beta]]-crystallins and monomeric [[gamma]]-crystallins form a superfamily of proteins and are an excellent example of how domain swapping can create dimers from monomers as a result of conformational differences in domain linkers. The 21 kDa [[gamma]]-crystallin family has two branches: the ubiquitous, highly conserved [[gamma]]S, and the more variable branch comprised of at least six members [[gamma]]A - [[gamma]]F in mammals. A predicted model of [[gamma]]S-crystallin shows that it differs from other [[gamma]]-crystallins mainly in the interface region between domains. In bovine lens [[gamma]]B and [[gamma]]D phase separate at low temperature whereas [[gamma]]E separates at body temperature and consequently is implicated in cold cataract. Our previous crystallographic studies on a single domain of [[gamma]]B show how sequence extensions effect domain interactions.

We will report on crystallographic studies of engineered crystalline. Complete [[gamma]]S-crystallin has resisted crystallization but the isolated N and C-terminal domains have. The C-terminal domain of , [[beta]]B2-crystallin has also been crystallized as well as a mutant [[gamma]]B crystallin with a [[gamma]]E linker. These studies will aid in defining the role of linkers, extensions, and surface hydrophobic patches in determining domain interactions in crystalline.