Protein–protein interaction sites are hot spots for disease-associated nonsynonymous SNPs
✍ Scribed by Alessia David; Rozami Razali; Mark N. Wass; Michael J.E. Sternberg
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 199 KB
- Volume
- 33
- Category
- Article
- ISSN
- 1059-7794
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✦ Synopsis
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.