Protein-protein interaction sites are hot spots for disease-associated nonsynonymous SNPs

David, Alessia and Razali, Rozami and Wass, Mark N. and Sternberg, Michael J.E. (2012) Protein-protein interaction sites are hot spots for disease-associated nonsynonymous SNPs. Human Mutation, 33 (2). pp. 359-363. ISSN 1059-7794. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1002/humu.21656

Abstract

Many nonsynonymous single nucleotide polymorphisms (nsSNPs) are disease causing due to effects at protein-protein interfaces. We have integrated a database of the three-dimensional (3D) structures of human protein/protein complexes and the humsavar database of nsSNPs. We analyzed the location of nsSNPS in terms of their location in the protein core, at protein-protein interfaces, and on the surface when not at an interface. Disease-causing nsSNPs that do not occur in the protein core are preferentially located at protein-protein interfaces rather than surface noninterface regions when compared to random segregation. The disruption of the protein-protein interaction can be explained by a range of structural effects including the loss of an electrostatic salt bridge, the destabilization due to reduction of the hydrophobic effect, the formation of a steric clash, and the introduction of a proline altering the main-chain conformation.

Item Type: Article
Uncontrolled keywords: nonsynonymous SNPs;protein structure;interactome;bioinformatics
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Mark Wass
Date Deposited: 09 Oct 2012 11:01
Last Modified: 06 Jun 2013 15:35
Resource URI: http://kar.kent.ac.uk/id/eprint/31430 (The current URI for this page, for reference purposes)
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