Unknown

Dataset Information

0

NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G protein-coupled receptor.


ABSTRACT: The corticotropin-releasing factor (CRF) ligand family has diverse effects on the CNS, including the modulation of the stress response. The ligands' effects are mediated by binding to CRF G protein-coupled receptors. We have determined the 3D NMR structure of the N-terminal extracellular domain (ECD1) of the mouse CRF receptor 2beta, which is the major ligand recognition domain, and identified its ligand binding site by chemical-shift perturbation experiments. The fold is identified as a short consensus repeat (SCR), a common protein interaction module. Mutagenesis reveals the integrity of the hormone-binding site in the full-length receptor. This study proposes that the ECD1 captures the C-terminal segment of the ligand, whose N terminus then penetrates into the transmembrane region of the receptor to initiate signaling. Key residues of SCR in the ECD1 are conserved in the G protein-coupled receptor subfamily, suggesting the SCR fold in all of the ECD1s of this subfamily.

SUBMITTER: Grace CR 

PROVIDER: S-EPMC516482 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G protein-coupled receptor.

Grace Christy R R CR   Perrin Marilyn H MH   DiGruccio Michael R MR   Miller Charleen L CL   Rivier Jean E JE   Vale Wylie W WW   Riek Roland R  

Proceedings of the National Academy of Sciences of the United States of America 20040823 35


The corticotropin-releasing factor (CRF) ligand family has diverse effects on the CNS, including the modulation of the stress response. The ligands' effects are mediated by binding to CRF G protein-coupled receptors. We have determined the 3D NMR structure of the N-terminal extracellular domain (ECD1) of the mouse CRF receptor 2beta, which is the major ligand recognition domain, and identified its ligand binding site by chemical-shift perturbation experiments. The fold is identified as a short c  ...[more]

Similar Datasets

| S-EPMC2866279 | biostudies-literature
| S-EPMC1829229 | biostudies-literature
| S-EPMC4504729 | biostudies-literature
| S-EPMC3817388 | biostudies-literature
| S-EPMC3203757 | biostudies-literature
| S-EPMC5551398 | biostudies-literature
| S-EPMC3098264 | biostudies-literature
| S-EPMC6333900 | biostudies-literature
| S-EPMC2242605 | biostudies-literature
| S-EPMC2865338 | biostudies-literature