Genetic Analysis of the First and Third Extracellular Loops of the C5a Receptor Reveals an Essential Wxfg Motif in the First Loop.
From: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
The Journal of biological chemistry
- Publish Date: Apr 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 17
- Pages: 12010-9
- Medium: Print
- Language: English
- Citation (JAMA): Klco Jeffery M, Nikiforovich Gregory V, Baranski Thomas J, et al. Genetic Analysis of the First and Third Extracellular Loops of the C5a Receptor Reveals an Essential Wxfg Motif in the First Loop.. J. Biol. Chem. Apr 2006;281:12010-9
Abstract
The extracellular loops of G protein-coupled receptors (GPCRs) frequently contain binding sites for peptide ligands. However, the mechanism of receptor activation following ligand binding and the influence of the extracellular loops in other aspects of receptor function are poorly understood. Here we report a structure-function analysis of the first and third extracellular loops of the human C5a receptor, a GPCR that binds a 74-amino acid peptide ligand. Amino acid substitutions were randomly incorporated into each loop, and functional receptors were identified in yeast. The first extracellular loop contains a large number of positions that cannot tolerate amino acid substitutions, especially residues within the WXFG motif found in many rhodopsin-like GPCRs, yet disruption of these residues does not alter C5a binding affinity. These results demonstrate an unanticipated role for the first extracellular loop, and the WXFG motif in particular, in ligand-mediated activation of the C5a receptor. This motif likely serves a similar role in other GPCRs. The third extracellular loop, in contrast, contains far fewer preserved residues and appears to play a less essential role in receptor activation.
Mesh Headings (Keywords): Amino Acid Motifs, Amino Acid Sequence, Amino Acid Substitution, Binding Sites, Cells, Cultured, Humans, Kidney, Ligands, Membrane Proteins, Models, Molecular, Molecular Sequence Data, Mutation, Peptide Fragments, Protein Binding, Protein Conformation, Receptors, Complement, Saccharomyces cerevisiae, Sequence Homology, Amino Acid
Check for Full Text / PubMed Unique Identifier (PMID): 16505476
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.