Mandal Taraknath, Lough Wilson, Spagnolie Saverio E, Audhya Anjon, Cui Qiang
Department of Chemistry, Boston University, Boston, Massachusetts.
Department of Mathematics.
Biophys J. 2020 Mar 24;118(6):1333-1343. doi: 10.1016/j.bpj.2020.01.033. Epub 2020 Feb 4.
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.
转运所需的内体分选复合体（ESCRT）机制执行整个细胞中许多生物过程所需的膜分裂反应。近年来，ESCRT如何结合并使细胞膜变形并最终产生囊泡一直是活跃的研究课题。在本研究中，我们使用全原子分子动力学模拟来仔细研究由Vps32原体组成的细丝的结构细节，Vps32原体是ESCRT-III复合体的主要成分。模拟结果表明，单体之间的疏水相互作用和静电相互作用都有助于维持细丝的结构稳定性，该细丝呈现出固有的弯曲和扭曲。我们的研究结果表明，随着细丝在膜表面上伸长，弯曲和扭曲应力的积累可能有助于膜内陷的驱动力。细丝暴露了一个大的阳离子表面，该表面可感知膜中带负电荷的脂质，并且单体的N端两亲性螺旋不仅充当膜锚，还会产生明显的正膜曲率。综合所有结果，我们讨论了一种由ESCRT-III驱动的膜内陷的合理机制。
