EMD-20246

Single-particle
3.2 Å
EMD-20246 Deposition: 26/05/2019
Map released: 24/07/2019
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-20246

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

EMD-20246

Single-particle
3.2 Å
EMD-20246 Deposition: 26/05/2019
Map released: 24/07/2019
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Mus musculus
Sample: TMEM16F with calcium bound
Fitted models: 6p48 (Avg. Q-score: 0.383)
Raw data: EMPIAR-10280

Deposition Authors: Feng S, Dang S
Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling.
Feng S, Dang S , Han TW, Ye W, Jin P, Cheng T, Li J, Jan YN, Jan LY, Cheng Y
(2019) Cell Rep , 28 , 567 - 579.e4
PUBMED: 31291589
DOI: doi:10.1016/j.celrep.2019.06.023
ISSN: 2211-1247
Abstract:
As a Ca2+-activated lipid scramblase and ion channel that mediates Ca2+ 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 PIP2-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 Ca2+ 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.