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Wrapping the alpha-crystallin domain fold in a chaperone assembly

Stamler, R. and Kappé, G. and Boelens, W.C. and Slingsby, Christine (2005) Wrapping the alpha-crystallin domain fold in a chaperone assembly. Journal of Molecular Biology 353 (1), pp. 68-79. ISSN 0022-2836.

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Official URL: http://dx.doi.org/10.1016/j.jmb.2005.08.025

Abstract

Small heat shock proteins (sHsps) are oligomers that perform a protective function by binding denatured proteins. Although ubiquitous, they are of variable sequence except for a C-terminal similar to 90-residue "alpha-crystallin domain". Unlike larger stress response chaperones, sHsps are ATP-independent and generally form polydisperse assemblies. One proposed mechanism of action involves these assemblies breaking into smaller subunits in response to stress, before binding unfolding substrate and reforming into larger complexes. Two previously solved non-metazoan sHsp multimers are built from dimers formed by domain swapping between the alpha-crystallin domains,. adding to evidence that the smaller subunits are dimers. Here, the 2.5 angstrom resolution structure of an sHsp from the parasitic flatworm Taenia saginata Tsp36, the first metazoan crystal structure, shows a new mode of dimerization involving N-terminal regions, which differs from that seen for non-metazoan sHsps. Sequence differences in the a-crystallin domains between metazoans and nonmetazoans are critical to the different mechanism of dimerization, suggesting that some structural features seen for Tsp36 may be generalized to other metazoan sHsps. The structure also indicates scope for flexible assembly of subunits, supporting the proposed process of oligomer breakdown, substrate binding and reassembly as the chaperone mechanism. It further shows how sHsps can bind coil and secondary structural elements by wrapping them around the alpha-crystallin domain. The structure also illustrates possible roles for conserved residues associated with disease, and suggests a mechanism for the sHsp-related pathogenicity of some flatworm infections. Tsp36, like other flatworm sHsps, possesses two divergent sHsp repeats per monomer. Together with the two previously solved structures, a total of four alpha-crystallin domain structures are now available, giving a better definition of domain boundaries for sHsps.

Item Type: Article
Keyword(s) / Subject(s): alpha-crystallin, Echinococcus multilocularis, molecular chaperone, Schistosoma mansoni, small heat shock protein, heat-shock-protein, major egg antigen, B-crystallin, molecular chaperone, oligomer formation, subunit exchange, binding, Hsp25, disaggregation, cytoskeleton
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Sandra Plummer
Date Deposited: 24 Jan 2006
Last Modified: 17 Apr 2013 12:32
URI: http://eprints.bbk.ac.uk/id/eprint/303

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