Cargando…
Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors
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 (7T...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221663/ https://www.ncbi.nlm.nih.gov/pubmed/22132149 http://dx.doi.org/10.1371/journal.pone.0027813 |
_version_ | 1782217119801278464 |
---|---|
author | Fatakia, Sarosh N. Costanzi, Stefano Chow, Carson C. |
author_facet | Fatakia, Sarosh N. Costanzi, Stefano Chow, Carson C. |
author_sort | Fatakia, Sarosh N. |
collection | PubMed |
description | 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 molecule-activated 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. |
format | Online Article Text |
id | pubmed-3221663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32216632011-11-30 Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors Fatakia, Sarosh N. Costanzi, Stefano Chow, Carson C. PLoS One Research Article 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 molecule-activated 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. Public Library of Science 2011-11-21 /pmc/articles/PMC3221663/ /pubmed/22132149 http://dx.doi.org/10.1371/journal.pone.0027813 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Fatakia, Sarosh N. Costanzi, Stefano Chow, Carson C. Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors |
title | Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors |
title_full | Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors |
title_fullStr | Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors |
title_full_unstemmed | Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors |
title_short | Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors |
title_sort | molecular evolution of the transmembrane domains of g protein-coupled receptors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221663/ https://www.ncbi.nlm.nih.gov/pubmed/22132149 http://dx.doi.org/10.1371/journal.pone.0027813 |
work_keys_str_mv | AT fatakiasaroshn molecularevolutionofthetransmembranedomainsofgproteincoupledreceptors AT costanzistefano molecularevolutionofthetransmembranedomainsofgproteincoupledreceptors AT chowcarsonc molecularevolutionofthetransmembranedomainsofgproteincoupledreceptors |