5II0

Crystal structure of the human calcitonin receptor ectodomain in complex with a truncated salmon calcitonin analogue

Summary for 5II0

• Entry DOI: 10.2210/pdb5ii0/pdb
• Descriptor: Calcitonin receptor, Calcitonin, SODIUM ION, ... (5 entities in total)
• Functional Keywords: calcitonin, g protein coupled receptor, peptide hormone, ectodomain, hormone
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P30988
• Total number of polymer chains: 6
• Total formula weight: 51758.57

Authors

Johansson, E.,Reedtz-Runge, S. (deposition date: 2016-03-01, release date: 2016-05-11, Last modification date: 2024-01-10)

Primary citation

Johansson, E.,Hansen, J.L.,Hansen, A.M.,Shaw, A.C.,Becker, P.,Schaffer, L.,Reedtz-Runge, S.
Type II Turn of Receptor-bound Salmon Calcitonin Revealed by X-ray Crystallography.
J.Biol.Chem., 291:13689-13698, 2016

PubMed Abstract: Calcitonin is a peptide hormone consisting of 32 amino acid residues and the calcitonin receptor is a Class B G protein-coupled receptor (GPCR). The crystal structure of the human calcitonin receptor ectodomain (CTR ECD) in complex with a truncated analogue of salmon calcitonin ([BrPhe(22)]sCT(8-32)) has been determined to 2.1-Å resolution. Parallel analysis of a series of peptide ligands showed that the rank order of binding of the CTR ECD is identical to the rank order of binding of the full-length CTR, confirming the structural integrity and relevance of the isolated CTR ECD. The structure of the CTR ECD is similar to other Class B GPCRs and the ligand binding site is similar to the binding site of the homologous receptors for the calcitonin gene-related peptide (CGRP) and adrenomedulin (AM) recently published (Booe, J. M., Walker, C. S., Barwell, J., Kuteyi, G., Simms, J., Jamaluddin, M. A., Warner, M. L., Bill, R. M., Harris, P. W., Brimble, M. A., Poyner, D. R., Hay, D. L., and Pioszak, A. A. (2015) Mol. Cell 58, 1040-1052). Interestingly the receptor-bound structure of the ligand [BrPhe(22)]sCT(8-32) differs from the receptor-bound structure of the homologous ligands CGRP and AM. They all adopt an extended conformation followed by a C-terminal β turn, however, [BrPhe(22)]sCT(8-32) adopts a type II turn (Gly(28)-Thr(31)), whereas CGRP and AM adopt type I turns. Our results suggest that a type II turn is the preferred conformation of calcitonin, whereas a type I turn is the preferred conformation of peptides that require RAMPs; CGRP, AM, and amylin. In addition the structure provides a detailed molecular explanation and hypothesis regarding ligand binding properties of CTR and the amylin receptors.

PubMed: 27189946
DOI: 10.1074/jbc.M116.726034

Experimental method

X-RAY DIFFRACTION (2.097 Å)