8BC1

Cryo-EM Structure of Ca2+-bound mTMEM16F F518A_Q623A mutant in GDN

8BC1 の概要

• エントリーDOI: 10.2210/pdb8bc1/pdb
• EMDBエントリー: 15959
• 分子名称: Anoctamin-6,mTMEM16F, CALCIUM ION (2 entities in total)
• 機能のキーワード: lipid scramblase, ion channel, membrane protein, blood coagulation, viral entry, cell fusion
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 226901.44

構造登録者

Arndt, M.,Alvadia, C.,Straub, M.S.,Clerico-Mosina, V.,Paulino, C.,Dutzler, R. (登録日: 2022-10-14, 公開日: 2022-11-16, 最終更新日: 2024-11-13)

主引用文献

Arndt, M.,Alvadia, C.,Straub, M.S.,Clerico Mosina, V.,Paulino, C.,Dutzler, R.
Structural basis for the activation of the lipid scramblase TMEM16F.
Nat Commun, 13:6692-6692, 2022

PubMed Abstract: TMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in response to an increase in intracellular Ca. However, the mechanism of how the protein facilitates both processes has remained elusive. Here we investigate the basis for TMEM16F activation. In a screen of residues lining the proposed site of conduction, we identify mutants with strongly activating phenotype. Structures of these mutants determined herein by cryo-electron microscopy show major rearrangements leading to the exposure of hydrophilic patches to the membrane, whose distortion facilitates lipid diffusion. The concomitant opening of a pore promotes ion conduction in the same protein conformation. Our work has revealed a mechanism that is distinct for this branch of the family and that will aid the development of a specific pharmacology for a promising drug target.

PubMed: 36335104
DOI: 10.1038/s41467-022-34497-x

実験手法

ELECTRON MICROSCOPY (2.93 Å)