Generic GPCR residue numbers - aligning topology maps while minding the gaps

Vignir Isberg; Chris de Graaf; Andrea Bortolato; Vadim Cherezov; Vsevolod Katritch; Fiona H Marshall; Stefan Mordalski; Jean-Philippe Pin; Raymond C Stevens; Gerrit Vriend; David E Gloriam

doi:10.1016/j.tips.2014.11.001

Generic GPCR residue numbers - aligning topology maps while minding the gaps

Trends Pharmacol Sci. 2015 Jan;36(1):22-31. doi: 10.1016/j.tips.2014.11.001. Epub 2014 Dec 22.

Authors

Affiliations

¹ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems, VU University Amsterdam, The Netherlands.
³ Heptares Therapeutics Ltd, Welwyn Garden City, UK.
⁴ The Bridge@USC, Department of Chemistry, University of Southern California, Los Angeles, CA 90089 USA.
⁵ The Bridge@USC, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089 USA.
⁶ Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
⁷ Institute of Functional Genomics, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 5203, Universities Montpellier, Montpellier, France; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 661, Montpellier, France.
⁸ The Bridge@USC, Department of Chemistry, University of Southern California, Los Angeles, CA 90089 USA; The Bridge@USC, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089 USA.
⁹ Centre for Molecular and Biomolecular Informatics (CMBI), Radboudumc, Nijmegen, The Netherlands.
¹⁰ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: [email protected].

Abstract

Generic residue numbers facilitate comparisons of, for example, mutational effects, ligand interactions, and structural motifs. The numbering scheme by Ballesteros and Weinstein for residues within the class A GPCRs (G protein-coupled receptors) has more than 1100 citations, and the recent crystal structures for classes B, C, and F now call for a community consensus in residue numbering within and across these classes. Furthermore, the structural era has uncovered helix bulges and constrictions that offset the generic residue numbers. The use of generic residue numbers depends on convenient access by pharmacologists, chemists, and structural biologists. We review the generic residue numbering schemes for each GPCR class, as well as a complementary structure-based scheme, and provide illustrative examples and GPCR database (GPCRDB) web tools to number any receptor sequence or structure.

Keywords: G protein-coupled receptor; ligand binding; mutational effects; sequence alignments; structural motifs.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Humans
Protein Conformation
Receptors, G-Protein-Coupled / chemistry*
Receptors, G-Protein-Coupled / classification
Sequence Alignment
Sequence Analysis, Protein

Substances

Receptors, G-Protein-Coupled

Abstract

Publication types

MeSH terms

Substances

Grants and funding