1U34

3D NMR structure of the first extracellular domain of CRFR-2beta, a type B1 G-protein coupled receptor

Summary for 1U34

• Entry DOI: 10.2210/pdb1u34/pdb
• Descriptor: Corticotropin releasing factor receptor 2 (1 entity in total)
• Functional Keywords: beta sheets and loops, signaling protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Cell membrane; Multi-pass membrane protein: Q60748
• Total number of polymer chains: 1
• Total formula weight: 13626.10

Authors

Grace, C.R.,Perrin, M.H.,DiGruccio, M.R.,Miller, C.L.,Rivier, J.E.,Vale, W.W.,Riek, R. (deposition date: 2004-07-20, release date: 2004-09-07, Last modification date: 2024-11-20)

Primary citation

Grace, C.R.,Perrin, M.H.,DiGruccio, M.R.,Miller, C.L.,Rivier, J.E.,Vale, W.W.,Riek, R.
NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G protein-coupled receptor
Proc.Natl.Acad.Sci.USA, 101:12836-12841, 2004

PubMed 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.

PubMed: 15326300
DOI: 10.1073/pnas.0404702101

Experimental method

SOLUTION NMR