7VVM

PTH-bound human PTH1R in complex with Gs (class3)

7VVM の概要

• エントリーDOI: 10.2210/pdb7vvm/pdb
• EMDBエントリー: 32144
• 分子名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: g protein-coupled receptor, membrane protein, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 163953.59

構造登録者

Kobayashi, K.,Kusakizako, T.,Miyauchi, H.,Tomita, A.,Kobayashi, K.,Shihoya, W.,Yamashita, K.,Nishizawa, T.,Kato, H.E.,Nureki, O. (登録日: 2021-11-06, 公開日: 2022-08-03, 最終更新日: 2024-10-30)

主引用文献

Kobayashi, K.,Kawakami, K.,Kusakizako, T.,Miyauchi, H.,Tomita, A.,Kobayashi, K.,Shihoya, W.,Yamashita, K.,Nishizawa, T.,Kato, H.E.,Inoue, A.,Nureki, O.
Endogenous ligand recognition and structural transition of a human PTH receptor.
Mol.Cell, 82:3468-3483.e5, 2022

PubMed Abstract: Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP.

PubMed: 35932760
DOI: 10.1016/j.molcel.2022.07.003

実験手法

ELECTRON MICROSCOPY (3.2 Å)