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Stability of domain structures in multi-domain proteins

Bhaskara, Ramachandra M and Srinivasan, Narayanaswamy (2011) Stability of domain structures in multi-domain proteins. In: Scientific Reports, 1 .

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Official URL: http://www.nature.com/srep/2011/110718/srep00040/f...

Abstract

Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Nature Publishing Group.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 17 Nov 2011 09:41
Last Modified: 17 Nov 2011 09:41
URI: http://eprints.iisc.ac.in/id/eprint/42101

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