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Molecular Evolution of the Transmembrane Domains of (2010)
BibTeX
@MISC{Receptors10molecularevolution,
author = {G Protein-coupled Receptors and Sarosh N. Fatakia},
title = {Molecular Evolution of the Transmembrane Domains of},
year = {2010}
}
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Abstract
G protein-coupled receptors (GPCRs) are a superfamily of integral membrane proteins vital for signaling and are important targets for pharmaceutical intervention in humans. Previously, we identified a group of ten amino acid positions (called key positions), within the seven transmembrane domain (7TM) interhelical region, which had high mutual information with each other and many other positions in the 7TM. Here, we estimated the evolutionary selection pressure at those key positions. We found that the key positions of receptors for small molecule natural ligands were under strong negative selection. Receptors naturally activated by lipids had weaker negative selection in general when compared to small moleculeactivated receptors. Selection pressure varied widely in peptide-activated receptors. We used this observation to predict that a subgroup of orphan GPCRs not under strong selection may not possess a natural small-molecule ligand. In the subgroup of MRGX1-type GPCRs, we identified a key position, along with two non-key positions, under statistically significant positive selection.
Keyphrases
transmembrane domain key position molecular evolution mrgx1-type gpcrs orphan gpcrs pharmaceutical intervention natural small-molecule ligand peptide-activated receptor evolutionary selection pressure high mutual information small moleculeactivated receptor important target integral membrane protein strong selection selection pressure strong negative selection many position protein-coupled receptor ten amino acid position small molecule natural ligand significant positive selection non-key position interhelical region negative selection
