+検索条件
-Structure paper
タイトル | Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM. |
---|---|
ジャーナル・号・ページ | Elife, Vol. 8, Year 2019 |
掲載日 | 2019年2月21日 |
著者 | Valeria Kalienkova / Vanessa Clerico Mosina / Laura Bryner / Gert T Oostergetel / Raimund Dutzler / Cristina Paulino / |
PubMed 要旨 | Scramblases catalyze the movement of lipids between both leaflets of a bilayer. Whereas the X-ray structure of the protein nhTMEM16 has previously revealed the architecture of a Ca-dependent lipid ...Scramblases catalyze the movement of lipids between both leaflets of a bilayer. Whereas the X-ray structure of the protein nhTMEM16 has previously revealed the architecture of a Ca-dependent lipid scramblase, its regulation mechanism has remained elusive. Here, we have used cryo-electron microscopy and functional assays to address this question. Ca-bound and Ca-free conformations of nhTMEM16 in detergent and lipid nanodiscs illustrate the interactions with its environment and they reveal the conformational changes underlying its activation. In this process, Ca binding induces a stepwise transition of the catalytic subunit cavity, converting a closed cavity that is shielded from the membrane in the absence of ligand, into a polar furrow that becomes accessible to lipid headgroups in the Ca-bound state. Additionally, our structures demonstrate how nhTMEM16 distorts the membrane at both entrances of the subunit cavity, thereby decreasing the energy barrier for lipid movement. |
リンク | Elife / PubMed:30785398 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.6 - 3.8 Å |
構造データ | EMDB-4587, PDB-6qm4: EMDB-4588, PDB-6qm5: EMDB-4589, PDB-6qm6: EMDB-4592, PDB-6qm9: |
化合物 | ChemComp-CA: |
由来 |
|
キーワード | MEMBRANE PROTEIN / lipid scrambles / TMEM16 |