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-Structure paper
タイトル | Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling. |
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ジャーナル・号・ページ | Cell Rep, Vol. 28, Issue 2, Page 567-579.e4, Year 2019 |
掲載日 | 2019年7月9日 |
著者 | Shengjie Feng / Shangyu Dang / Tina Wei Han / Wenlei Ye / Peng Jin / Tong Cheng / Junrui Li / Yuh Nung Jan / Lily Yeh Jan / Yifan Cheng / |
PubMed 要旨 | 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 ...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. |
リンク | Cell Rep / PubMed:31291589 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 3.9 Å |
構造データ | EMDB-20244, PDB-6p46: EMDB-20245, PDB-6p47: EMDB-20246, PDB-6p48: EMDB-20247, PDB-6p49: |
化合物 | ChemComp-CA: |
由来 |
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キーワード | MEMBRANE PROTEIN / TMEM16F / scramblase |