期刊
FASEB JOURNAL
卷 26, 期 8, 页码 3273-3281出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.12-203737
关键词
structure-function relationship; evolution; mutagenesis; nucleotide receptor
资金
- Deutsche Forschungsgemeinschaft [FOR 748, Scho 624/7-1]
- Medical Faculty, University of Leipzig
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 P2Y12 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.-Coster, M., Wittkopf, D., Kreuchwig, A., Kleinau, G., Thor, D., Krause, G., Schoneberg, T. Using ortholog sequence data to predict the functional relevance of mutations in G-protein-coupled receptors. FASEB J. 26, 3273-3281 (2012). www.fasebj.org
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据