HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: ps.062659107v1 16/4/615    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smith, M. A. Articles by Slingsby, C. Search for Related Content PubMed PubMed Citation Articles by Smith, M. A. Articles by Slingsby, C. Social Bookmarking                   What's this?

Mutation of interfaces in domain-swapped human B2-crystallin

Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX, United Kingdom

(RECEIVED November 8, 2006; FINAL REVISION December 13, 2006; ACCEPTED December 19, 2006)

The superfamily of eye lens -crystallins is highly modularized, with Greek key motifs being used to form symmetric domains. Sequences of monomeric -crystallins and oligomeric -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 B2-crystallin to form a solution dimer. However, the 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 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 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 -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.

Keywords: B1-crystallin; cataract; crystal structure; domain swapping; eye lens; Greek key; oligomer assembly

CiteULike

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				I. A. Mills, S. L. Flaugh, M. S. Kosinski-Collins, and J. A. King Folding and stability of the isolated Greek key domains of the long-lived human lens proteins {gamma}D-crystallin and {gamma}S-crystallin Protein Sci., November 1, 2007; 16(11): 2427 - 2444. [Abstract] [Full Text] [PDF]