6OY3

nhTMEM16 L302A +Ca2+ in nanodiscs

6OY3 の概要

• エントリーDOI: 10.2210/pdb6oy3/pdb
• EMDBエントリー: 20221
• 分子名称: nhTMEM16, CALCIUM ION (2 entities in total)
• 機能のキーワード: tmem16, scramblase, lipid transport, anoactamin
• 由来する生物種: Nectria haematococca (strain 77-13-4 / ATCC MYA-4622 / FGSC 9596 / MPVI)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 166476.17

構造登録者

Falzone, M.,Lee, B.C.,Accardi, A. (登録日: 2019-05-14, 公開日: 2019-11-06, 最終更新日: 2024-03-20)

主引用文献

Khelashvili, G.,Falzone, M.E.,Cheng, X.,Lee, B.C.,Accardi, A.,Weinstein, H.
Dynamic modulation of the lipid translocation groove generates a conductive ion channel in Ca 2+ -bound nhTMEM16.
Nat Commun, 10:4972-4972, 2019

PubMed Abstract: Both lipid and ion translocation by Ca-regulated TMEM16 transmembrane proteins utilizes a membrane-exposed hydrophilic groove. Several conformations of the groove are observed in TMEM16 protein structures, but how these conformations form, and what functions they support, remains unknown. From analyses of atomistic molecular dynamics simulations of Ca-bound nhTMEM16 we find that the mechanism of a conformational transition of the groove from membrane-exposed to occluded from the membrane involves the repositioning of transmembrane helix 4 (TM4) following its disengagement from a TM3/TM4 interaction interface. Residue L302 is a key element in the hydrophobic TM3/TM4 interaction patch that braces the open-groove conformation, which should be changed by an L302A mutation. The structure of the L302A mutant determined by cryogenic electron microscopy (cryo-EM) reveals a partially closed groove that could translocate ions, but not lipids. This is corroborated with functional assays showing severely impaired lipid scrambling, but robust channel activity by L302A.

PubMed: 31672969
DOI: 10.1038/s41467-019-12865-4

実験手法

ELECTRON MICROSCOPY (4 Å)