Membrane Charge Directs the Outcome of F-BAR Domain Lipid Binding and Autoregulation.
Membrane Charge Directs the Outcome of F-BAR Domain Lipid Binding and Autoregulation.
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DOI：
10.1016/j.celrep.2015.11.044
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发表时间：
2015-12-22
期刊：
影响因子：
8.8
通讯作者：
Rodal AA
中科院分区：
文献类型：
--
作者：
Kelley CF;Messelaar EM;Eskin TL;Wang S;Song K;Vishnia K;Becalska AN;Shupliakov O;Hagan MF;Danino D;Sokolova OS;Nicastro D;Rodal AA
F-BAR结构域蛋白通过与带负电荷的磷脂相互作用并组装成更高阶的支架来调节和感知膜曲率。然而，控制这些相互作用的调节机制知之甚少。在这里，我们表明，果蝇神经残骸（Nwk）是自动调节的C-末端SH 3结构域模块，直接与其F-BAR结构域相互作用。令人惊讶的是，这种自动调节并不介导膜重塑的简单“开关”。相反，孤立的Nwk F-BAR结构域有效地组装成更高阶的结构，并使膜仅在有限的膜负电荷范围内变形，并且自动调节提高了该范围。因此，自动调节可以减少膜结合或促进更高阶的组装，这取决于局部细胞膜的组成。我们的研究结果揭示了一个意想不到的机制，脂质成分指导膜重塑。
F-BAR domain proteins regulate and sense membrane curvature by interacting with negatively charged phospholipids and assembling into higher-order scaffolds. However, regulatory mechanisms controlling these interactions are poorly understood. Here, we show that Drosophila Nervous Wreck (Nwk) is autoregulated by a C-terminal SH3 domain module that interacts directly with its F-BAR domain. Surprisingly, this autoregulation does not mediate a simple “on-off” switch for membrane remodeling. Instead, the isolated Nwk F-BAR domain efficiently assembles into higher-order structures and deforms membranes only within a limited range of negative membrane charge, and autoregulation elevates this range. Thus, autoregulation could either reduce membrane binding or promote higher order assembly, depending on local cellular membrane composition. Our findings uncover an unexpected mechanism by which lipid composition directs membrane remodeling.