HIGH-RESOLUTION STRUCTURE OF AN OLIGOMERIC EYE LENS BETA-CRYSTALLIN - LOOPS, ARCHES, LINKERS AND INTERFACES IN BETA-B2 DIMER COMPARED TO A MONOMERIC GAMMA-CRYSTALLIN

β-Crystallins are polydisperse, oligomeric structural proteins that have a major role in forming the high refractive index of the eye lens. Using single crystal X-ray crystallography with molecular replacement, the structure of βB2 dimer has been solved at 2·1 Å resolution. Each subunit comprises an N and C-terminal domain that are very similar and each domain is formed from two similar "Greek key" motifs related by a local dyad. Sequence differences in the internally quadruplicated molecules, analysed in terms of their β-sheets, hairpins and arches, give rise to structural differences in the motifs. Whereas the related family of γ-crystallins are monomers, β-crystallins are always oligomers. In the βB2 subunit, the domains, each comprising two motifs, are separated by an extended linking peptide. A crystallographic 2-fold axis relates the two subunits of the dimer so that the N-terminal domain of one subunit of βB2 and the C-terminal domain of the symmetry-related subunit are topologically equivalent to the two covalently connected domains of γB-crystallin. The intersubunit domain interface is very similar to the intradomain interface of γB, although many sequence differences have resulted in an increase in polar interactions between domains in βB2. Comparison of the structures of βB2 and γB-crystallins shows that the two families differ largely in the conformation of their connecting peptides. A further extensive lattice contact indicates a tetramer with 222 symmetry. The ways in which insertions and extensions in the β-crystallin effect oligomer interactions are described. The two kinds of crystallin are analysed for structural features that account for their different stabilities. These studies are a basis for understanding formation of higher aggregates in the lens. © 1991.