6P49

Cryo-EM structure of calcium-bound TMEM16F in nanodisc with supplement of PIP2 in Cl2

Summary for 6P49

• Entry DOI: 10.2210/pdb6p49/pdb
• EMDB information: 20244 20245 20246 20247
• Descriptor: Anoctamin-6, CALCIUM ION (2 entities in total)
• Functional Keywords: tmem16f, scramblase, membrane protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 212815.61

Authors

Feng, S.,Dang, S.,Han, T.W.,Ye, W.,Jin, P.,Cheng, T.,Li, J.,Jan, Y.N.,Jan, L.Y.,Cheng, Y. (deposition date: 2019-05-26, release date: 2019-07-24, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.3 Å)