Structural basis for phospholipid scrambling in the TMEM16 family
Structural basis for phospholipid scrambling in the TMEM16 family
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DOI：
10.1016/j.sbi.2016.05.020
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发表时间：
2016-08-01
影响因子：
6.8
通讯作者：
Dutzler, Raimund
中科院分区：
文献类型：
--
作者：
Brunner, Janine D.;Schenck, Stephan;Dutzler, Raimund
激活后，脂质乱序酶通过催化小叶之间的脂质翻转，以ATP非依赖性方式消除膜的脂质不对称性。这些蛋白质的分子身份长期以来一直不清楚，但近年来已发现TMEM16蛋白质家族构成Ca 2+激活的乱序酶。最近，真菌TMEM16同源物的X射线结构提供了深入了解这个蛋白质家族的结构和潜在的扰乱机制。该蛋白质形成同源二聚体，每个亚基含有跨膜亲水裂缝。该区域具有足够的尺寸以在其穿过膜的途中容纳极性头基，因此可以降低脂质在双层的两个小叶之间扩散的能量屏障。位于膜内的调节Ca2+结合位点邻近这个疏水裂缝负责激活的机制还不清楚。
Upon activation, lipid scramblases dissipate the lipid asymmetry of membranes, in an ATP-independent manner, by catalyzing flip-flop of lipids between the leaflets. The molecular identities of these proteins long remained obscure, but in recent years the TMEM16 family of proteins has been found to constitute Ca2+-activated scramblases. Recently, the X-ray structure of a fungal TMEM16 homologue has provided insight into the architecture of this protein family and into potential scrambling mechanisms. The protein forms homodimers with each subunit containing a membrane-spanning hydrophilic cleft. This region is of sufficient size to harbor polar headgroups on their way across the membrane and thus may lower the energetic barrier for the diffusion of lipids between the two leaflets of the bilayer. A regulatory Ca2+ binding site located within the membrane adjacent to this hydrophobic cleft is responsible for activation by yet unknown mechanisms.