THE X-RAY STRUCTURE OF A MUTANT EYE LENS BETA-B2-CRYSTALLIN WITH TRUNCATED SEQUENCE EXTENSIONS

beta-Crystallins are oligomeric eye lens proteins that are related to monomeric gamma-crystallins by domain swapping: like gamma-crystallins . they are comprised of two similar domains but they differ in having long sequence extensions, beta B2. a major component of beta-crystalli n oligomers, self-associates to a homodimer in solution. In two crysta l structures of native beta B2. the protein is a 222-symmetric tetrame r of eight domains. It has previously been shown that a mutant of rat beta B2-crystallin, in which the bulk of the N- and C-terminal sequenc e extensions has been deleted, assembles into dimers and tetramers. He re we present the 3.0 Angstrom resolution X-ray structure of the tetra mer, beta B2 Delta NCl. The mutant tetramer has a very similar set of domain interactions to the native structure. However, the structures d iffer in the relative orientation of the two sets of four domains. The paired N- and C-terminal domain interface, which is at the heart of t he dimer structure, is very similar to the native structure. However, the truncation of the C-terminal extension removes an important trypto phan residue, which prevents the extension from acting as a (non-coval ent) linker as it does in native beta B2. There is a knock-on structur al effect that removes a contact between extension and covalent linker , and this appears to cause a small twist in the linker that is amplif ied into a 20 degrees rotation between sets of paired domains.