Molecular Simulation of Mechanical Properties and Membrane Activities of the ESCRT-III Complexes
Molecular Simulation of Mechanical Properties and Membrane Activities of the ESCRT-III Complexes
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ESCRT-III络合物力学性质和膜活性的分子模拟
DOI：
10.1016/j.bpj.2020.01.033
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发表时间：
2020-03-24
影响因子：
3.4
通讯作者：
Cui, Qiang
中科院分区：
文献类型：
--
作者：
Mandal, Taraknath;Lough, Wilson;Cui, Qiang
转运所需的内体分选复合物（ESCRT）机制进行整个细胞中许多生物过程所需的膜断裂反应。ESCRTs如何结合和变形细胞膜，并最终产生囊泡，近年来一直是一个积极的研究问题。在这项研究中，我们使用完全原子分子动力学模拟来仔细研究由Vps 32原聚体组成的细丝的结构细节，Vps 32原聚体是ESCRT-III复合物的主要组成部分。模拟结果表明，单体之间的疏水和静电相互作用有助于保持长丝的结构稳定性，其表现出固有的弯曲和扭曲。我们的研究结果表明，弯曲和扭曲应力的积累，作为长丝在膜表面上伸长可能有助于膜内陷的驱动力。细丝暴露出一个大的阳离子表面，该表面可检测膜中带负电荷的脂质，单体的N-末端两亲性螺旋不仅充当膜锚，而且还产生显著的正膜曲率。综合所有结果，我们讨论了ESCRT-III驱动的膜内陷的合理机制。
The endosomal sorting complex required for transport (ESCRT) machinery carries out the membrane scission reactions that are required for many biological processes throughout cells. How ESCRTs bind and deform cellular membranes and ultimately produce vesicles has been a matter of active research in recent years. In this study, we use fully atomistic molecular dynamics simulations to scrutinize the structural details of a filament composed of Vps32 protomers, a major component of ESCRT-III complexes. The simulations show that both hydrophobic and electrostatic interactions between monomers help maintain the structural stability of the filament, which exhibits an intrinsic bend and twist. Our findings suggest that the accumulation of bending and twisting stresses as the filament elongates on the membrane surface likely contributes to the driving force for membrane invagination. The filament exposes a large cationic surface that senses the negatively charged lipids in the membrane, and the N-terminal amphipathic helix of the monomers not only acts as a membrane anchor but also generates significant positive membrane curvature. Taking all results together, we discuss a plausible mechanism for membrane invagination driven by ESCRT-III.