STRUCTURAL STUDIES OF EYE-LENS CRYSTALLINS

A. K. Basak., G. Wright. And C. Slingsby

Department of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, U. K.

Keywords: Crystallins, Eye-lens proteins.

The transparency and refraction of the eye-lens depends on the spatial organisation of a-, b- and g-crystallin proteins. a-crystallin is a giant macromolecule and belongs to the small hsp family of widespread occurrence, The monomeric g- and oligomeric b-crystallins form a superfamily of eye-lens proteins. Their fold contains multiple Greck key motifs, which are symmetrically organised into domains. The dimeric b-crystallins are related to monomeric g-crystallin by domain swapping. The 21kDa g-crystallin family has two branches, one is the highly conserved gS and the other is variable, gA-gF in mammals. The predicted model of gS, based on the structure of gB, shows that the domain interface in gS is somewhat different to that in other g-crystallins.

We will report on crystallographic studies of a number of engineered crystallins. These include gS C-terminal domain, circularly permuted two-domain bB2 and a mutant of gB crystallin with a gE linker. These studies will aid in defining the role of linker peptides and surface hydrophobic patches in domain interactions and will also show how domain permutation can convert intermolecular domain pairing to intramolecular pairing.