6AYG

Human Apo-TRPML3 channel at pH 4.8

6AYG の概要

• エントリーDOI: 10.2210/pdb6ayg/pdb
• EMDBエントリー: 7018 7019 7020
• 分子名称: Mucolipin-3 (1 entity in total)
• 機能のキーワード: ion channel, trp channel, lysosomal, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 258503.14

構造登録者

Zhou, X.,Li, M.,Su, D.,Jia, Q.,Li, H.,Li, X.,Yang, J. (登録日: 2017-09-08, 公開日: 2017-11-08, 最終更新日: 2024-03-13)

主引用文献

Zhou, X.,Li, M.,Su, D.,Jia, Q.,Li, H.,Li, X.,Yang, J.
Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states.
Nat. Struct. Mol. Biol., 24:1146-1154, 2017

PubMed Abstract: TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH. Here we present cryo-electron microscopy (cryo-EM) structures of human TRPML3 in the closed, agonist-activated, and low-pH-inhibited states, with resolutions of 4.06, 3.62, and 4.65 Å, respectively. The agonist ML-SA1 lodges between S5 and S6 and opens an S6 gate. A polycystin-mucolipin domain (PMD) forms a luminal cap. S1 extends into this cap, forming a 'gating rod' that connects directly to a luminal pore loop, which undergoes dramatic conformational changes in response to low pH. S2 extends intracellularly and interacts with several intracellular regions to form a 'gating knob'. These unique structural features, combined with the results of electrophysiological studies, indicate a new mechanism by which luminal pH and other physiological modulators such as PIP regulate TRPML3 by changing S1 and S2 conformations.

PubMed: 29106414
DOI: 10.1038/nsmb.3502

実験手法

ELECTRON MICROSCOPY (4.65 Å)