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

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

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)22-31
Number of pages10
JournalTrends in Pharmacological Sciences
Volume36
Issue number1
DOIs
Publication statusPublished - 2015

Keywords

  • G protein-coupled receptor
  • ligand binding
  • mutational effects
  • sequence alignments
  • structural motifs

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