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The X‐ray structure of a mutant eye lens βB2‐crystallin with truncated sequence extensions
Author(s) -
Norledge B.V.,
Slingsby C.,
Trinkl S.,
Jaenicke R.
Publication year - 1997
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560060802
Subject(s) - tetramer , crystallin , dimer , crystallography , linker , peptide sequence , stereochemistry , monomer , chemistry , mutant , protein structure , biochemistry , enzyme , polymer , organic chemistry , computer science , gene , operating system
β‐Crystallins are oligomeric eye lens proteins that are related to monomeric γ‐crystallins by domain swapping: like γ‐crystallins, they are comprised of two similar domains but they differ in having long sequence extensions. βB2, a major component of β‐crystallin oligomers, self‐associates to a homodimer in solution. In two crystal structures of native βB2, the protein is a 222‐symmetric tetramer of eight domains. It has previously been shown that a mutant of rat βB2‐crystallin, in which the bulk of the N‐ and C‐terminal sequence extensions has been deleted, assembles into dimers and tetramers. Here we present the 3.0 Å resolution X‐ray structure of the tetramer, βB2ΔNCI. The mutant tetramer has a very similar set of domain interactions to the native structure. However, the structures differ 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 the dimer structure, is very similar to the native structure. However, the truncation of the C‐terminal extension removes an important tryptophan residue, which prevents the extension from acting as a (non‐covalent) linker, as it does in native βB2. There is a knock‐on structural effect that removes a contact between extension and covalent linker, and this appears to cause a small twist in the linker that is amplified into a 20° rotation between sets of paired domains.