Format

Send to

Choose Destination
See comment in PubMed Commons below
FASEB J. 2012 Aug;26(8):3273-81. doi: 10.1096/fj.12-203737. Epub 2012 May 18.

Using ortholog sequence data to predict the functional relevance of mutations in G-protein-coupled receptors.

Author information

  • 1Molecular Biochemistry, Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany.

Abstract

Evaluating the functional relevance of naturally occurring gene variants usually requires experimental testing or is even impossible because of the lack of appropriate functional assays. Here we have analyzed whether comparative sequence data from orthologs are suitable to predict the functional relevance of mutations in a model protein, a G-protein-coupled receptor for ADP (P2Y(12)). The functional effect of every possible substitution at each amino acid position within a portion of P2Y(12) (1254 mutants) was individually determined. Sequence analysis of >70 P2Y(12) vertebrate orthologs revealed that this amino acid variability ensuring proper receptor function in vivo highly correlates (>90%) with the in vitro experimental data. Therefore, ortholog sequence data are helpful to predict the functional relevance of individual positions and mutations for P2Y(12). It is likely that similar conclusions may be extended for other GPCRs and conserved proteins as well.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk