6P48

Cryo-EM structure of calcium-bound TMEM16F in nanodisc with supplement of PIP2 in Cl1

6P48 の概要

• エントリーDOI: 10.2210/pdb6p48/pdb
• EMDBエントリー: 20244 20245 20246 20247
• 分子名称: Anoctamin-6, CALCIUM ION (2 entities in total)
• 機能のキーワード: tmem16f, scramblase, membrane protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 212815.61

構造登録者

Feng, S.,Dang, S.,Han, T.W.,Ye, W.,Jin, P.,Cheng, T.,Li, J.,Jan, Y.N.,Jan, L.Y.,Cheng, Y. (登録日: 2019-05-26, 公開日: 2019-07-24, 最終更新日: 2024-11-06)

主引用文献

Feng, S.,Dang, S.,Han, T.W.,Ye, W.,Jin, P.,Cheng, T.,Li, J.,Jan, Y.N.,Jan, L.Y.,Cheng, Y.
Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling.
Cell Rep, 28:567-579.e4, 2019

PubMed Abstract: As a Ca-activated lipid scramblase and ion channel that mediates Ca influx, TMEM16F relies on both functions to facilitate extracellular vesicle generation, blood coagulation, and bone formation. How a bona fide ion channel scrambles lipids remains elusive. Our structural analyses revealed the coexistence of an intact channel pore and PIP-dependent protein conformation changes leading to membrane distortion. Correlated to the extent of membrane distortion, many tightly bound lipids are slanted. Structure-based mutagenesis studies further reveal that neutralization of some lipid-binding residues or those near membrane distortion specifically alters the onset of lipid scrambling, but not Ca influx, thus identifying features outside of channel pore that are important for lipid scrambling. Together, our studies demonstrate that membrane distortion does not require open hydrophilic grooves facing the membrane interior and provide further evidence to suggest separate pathways for lipid scrambling and ion permeation.

PubMed: 31291589
DOI: 10.1016/j.celrep.2019.06.023

実験手法

ELECTRON MICROSCOPY (3.2 Å)