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

Alessia David, Rozaimi Mohamad Razali, Mark N. Wass, Michael J E Sternberg

Research output: Contribution to journalArticle

80 Citations (Scopus)

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. Diseasecausing 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.

Original languageEnglish
Pages (from-to)359-363
Number of pages5
JournalHuman Mutation
Volume33
Issue number2
DOIs
Publication statusPublished - 1 Feb 2012
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Proteins
Databases
Static Electricity
Proline
Salts

Keywords

  • Bioinformatics.
  • Interactome
  • Nonsynonymous snps
  • Protein structure

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Protein-protein interaction sites are hot spots for disease-associated nonsynonymous SNPs. / David, Alessia; Mohamad Razali, Rozaimi; Wass, Mark N.; Sternberg, Michael J E.

In: Human Mutation, Vol. 33, No. 2, 01.02.2012, p. 359-363.

Research output: Contribution to journalArticle

David, Alessia ; Mohamad Razali, Rozaimi ; Wass, Mark N. ; Sternberg, Michael J E. / Protein-protein interaction sites are hot spots for disease-associated nonsynonymous SNPs. In: Human Mutation. 2012 ; Vol. 33, No. 2. pp. 359-363.
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