5K5S

Crystal structure of the active form of human calcium-sensing receptor extracellular domain

5K5S の概要

• エントリーDOI: 10.2210/pdb5k5s/pdb
• 関連するPDBエントリー: 5K5T
• 分子名称: Extracellular calcium-sensing receptor, TRYPTOPHAN, PHOSPHATE ION, ... (6 entities in total)
• 機能のキーワード: venus flytrap module, cysteine-rich domain, homodimer, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 140698.29

構造登録者

Geng, Y.,Mosyak, L.,Kurinov, I.,Zuo, H.,Sturchler, E.,Cheng, T.C.,Subramanyam, P.,Brown, A.P.,Brennan, S.C.,Mun, H.-C.,Bush, M.,Chen, Y.,Nguyen, T.,Cao, B.,Chang, D.,Quick, M.,Conigrave, A.,Colecraft, H.M.,McDonald, P.,Fan, Q.R. (登録日: 2016-05-23, 公開日: 2016-08-03, 最終更新日: 2024-11-20)

主引用文献

Geng, Y.,Mosyak, L.,Kurinov, I.,Zuo, H.,Sturchler, E.,Cheng, T.C.,Subramanyam, P.,Brown, A.P.,Brennan, S.C.,Mun, H.C.,Bush, M.,Chen, Y.,Nguyen, T.X.,Cao, B.,Chang, D.D.,Quick, M.,Conigrave, A.D.,Colecraft, H.M.,McDonald, P.,Fan, Q.R.
Structural mechanism of ligand activation in human calcium-sensing receptor.
Elife, 5:-, 2016

PubMed Abstract: Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca(2+) homeostasis through the regulation of parathyroid hormone secretion. It functions as a disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation. Our structures reveal multiple binding sites for Ca(2+) and PO4(3-) ions. Both ions are crucial for structural integrity of the receptor. While Ca(2+) ions stabilize the active state, PO4(3-) ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.

PubMed: 27434672
DOI: 10.7554/eLife.13662

実験手法

X-RAY DIFFRACTION (2.6 Å)