期刊
PROTEIN SCIENCE
卷 16, 期 4, 页码 615-625出版社
WILEY
DOI: 10.1110/ps.062659107
关键词
beta B1-crystallin; cataract; crystal structure; domain swapping; eye lens; Greek key; oligomer assembly
资金
- Medical Research Council [G8303198] Funding Source: researchfish
- Medical Research Council [G8303198] Funding Source: Medline
- MRC [G8303198] Funding Source: UKRI
The superfamily of eye lens bg-crystallins is highly modularized, with Greek key motifs being used to form symmetric domains. Sequences of monomeric gamma-crystallins and oligomeric beta-crystallins fold into two domains that pair about a further conserved symmetric interface. Conservation of this assembly interface by domain swapping is the device adopted by family member beta B2-crystallin to form a solution dimer. However, the beta B1-crystallin solution dimer is formed from an interface used by the domain-swapped dimer to form a tetramer in the crystal lattice. Comparison of these two structures indicated an intriguing relationship between linker conformation, interface ion pair networks, and higher assembly. Here the X-ray structure of recombinant human beta B2-crystallin showed that domain swapping was determined by the sequence and not assembly conditions. The solution characteristics of mutants that were designed to alter an ion pair network at a higher assembly interface and a mutant that changed a proline showed they remained dimeric. X-ray crystallography showed that the dimeric mutants did not reverse domain swapping. Thus, the sequence of beta B2-crystallin appears well optimized for domain swapping. However, a charge-reversal mutation to the conserved domain-pairing interface showed drastic changes to solution behavior. It appears that the higher assembly of the beta gamma-crystallin domains has exploited symmetry to create diversity while avoiding aggregation. These are desirable attributes for proteins that have to exist at very high concentration for a very long time.
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