5WJ5

Human TRPML1 channel structure in closed conformation

5WJ5 の概要

• エントリーDOI: 10.2210/pdb5wj5/pdb
• EMDBエントリー: 8840 8841
• 分子名称: Mucolipin-1 (1 entity in total)
• 機能のキーワード: human trpml1, membrane 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: 260339.98

構造登録者

Schmiege, P.,Li, X. (登録日: 2017-07-21, 公開日: 2017-10-18, 最終更新日: 2024-11-20)

主引用文献

Schmiege, P.,Fine, M.,Blobel, G.,Li, X.
Human TRPML1 channel structures in open and closed conformations.
Nature, 550:366-370, 2017

PubMed Abstract: Transient receptor potential mucolipin 1 (TRPML1) is a Ca-releasing cation channel that mediates the calcium signalling and homeostasis of lysosomes. Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage disorder. Here we report two electron cryo-microscopy structures of full-length human TRPML1: a 3.72-Å apo structure at pH 7.0 in the closed state, and a 3.49-Å agonist-bound structure at pH 6.0 in an open state. Several aromatic and hydrophobic residues in pore helix 1, helices S5 and S6, and helix S6 of a neighbouring subunit, form a hydrophobic cavity to house the agonist, suggesting a distinct agonist-binding site from that found in TRPV1, a TRP channel from a different subfamily. The opening of TRPML1 is associated with distinct dilations of its lower gate together with a slight structural movement of pore helix 1. Our work reveals the regulatory mechanism of TRPML channels, facilitates better understanding of TRP channel activation, and provides insights into the molecular basis of mucolipidosis type IV pathogenesis.

PubMed: 29019983
DOI: 10.1038/nature24036

実験手法

ELECTRON MICROSCOPY (3.72 Å)