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PLoS One. 2015 Apr 16;10(4):e0123533. doi: 10.1371/journal.pone.0123533. eCollection 2015.

Sequence, structure and ligand binding evolution of rhodopsin-like G protein-coupled receptors: a crystal structure-based phylogenetic analysis.

Author information

1
Department of Biophysics, CAS-MPG Partner Institute for Computational Biology, Key Laboratory of Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China; Department of Biophysics, Ruhr-University Bochum, Bochum, Germany.
2
CAS-MPG Partner Institute for Computational Biology, Key Laboratory of Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China.

Abstract

G protein-coupled receptors (GPCRs) form the largest family of membrane receptors in the human genome. Advances in membrane protein crystallization so far resulted in the determination of 24 receptors available as high-resolution atomic structures. We performed the first phylogenetic analysis of GPCRs based on the available set of GPCR structures. We present a new phylogenetic tree of known human rhodopsin-like GPCR sequences based on this structure set. We can distinguish the three separate classes of small-ligand binding GPCRs, peptide binding GPCRs, and olfactory receptors. Analyzing different structural subdomains, we found that small molecule binding receptors most likely have evolved from peptide receptor precursors, with a rhodopsin/S1PR1 ancestor, most likely an ancestral opsin, forming the link between both classes. A light-activated receptor therefore seems to be the origin of the small molecule hormone receptors of the central nervous system. We find hints for a common evolutionary path of both ligand binding site and central sodium/water binding site. Surprisingly, opioid receptors exhibit both a binding cavity and a central sodium/water binding site similar to the one of biogenic amine receptors instead of peptide receptors, making them seemingly prone to bind small molecule ligands, e.g. opiates. Our results give new insights into the relationship and the pharmacological properties of rhodopsin-like GPCRs.

PMID:
25881057
PMCID:
PMC4399913
DOI:
10.1371/journal.pone.0123533
[Indexed for MEDLINE]
Free PMC Article

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