Format

Send to

Choose Destination
J Am Chem Soc. 2010 Jul 7;132(26):9049-57. doi: 10.1021/ja101868c.

Structure of a GPCR ligand in its receptor-bound state: leukotriene B4 adopts a highly constrained conformation when associated to human BLT2.

Author information

1
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université Paris-7, Institut de Biologie Physico-Chimique (FRC 550), 13 rue Pierre et Marie Curie, F-75005 Paris, France. laurent.catoire@ibpc.fr

Abstract

G protein-coupled receptors (GPCRs) are key players in signal recognition and cell communication and are among the most important targets for drug development. Direct structural information on the conformation of GPCR ligands bound to their receptors is scarce. Using a leukotriene receptor, BLT2, expressed under a perdeuterated form in Escherichia coli , purified in milligram amounts, and folded to its native state using amphipols, we have solved, by (1)H NMR, the structure of receptor-bound leukotriene B4 (LTB4). Upon binding, LTB4 adopts a highly constrained seahorse conformation, at variance with the free state, where it explores a wide range of conformations. This structure provides an experimentally determined template of a pro-inflammatory compound for further pharmacological studies. The novel approach used for its determination could prove powerful to investigate ligand binding to GPCRs and membrane proteins in general.

PMID:
20552979
DOI:
10.1021/ja101868c
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center