Blood Philip D, Voth Gregory A
Center for Biophysical Modeling and Simulation and Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15068-72. doi: 10.1073/pnas.0603917103. Epub 2006 Sep 28.
The process of membrane curvature generation by BAR (Bin/amphiphysin/Rvs) domains is thought to involve the plastering of the negatively charged cell membrane to the positively charged concave surface of the BAR domain. Recent work [Peter, B. J., et al. (2004) Science, 303,495-499; Masuda, M., et al. (2006) EMBO J. 25, 2889-2897; and Gallop, J. L., et al. (2006) EMBO J. 25, 2898-2910] has demonstrated the importance of the charged, crescent-shaped surface and the N-terminal amphipathic helices (present in N-BAR domains) for generating membrane curvature. These experiments suggest that curvature is generated by the synergistic action of the N-terminal helices embedding in the lipid bilayer and the charged crescent-shaped dimer acting to "scaffold" membrane curvature. Here, we present atomistic molecular dynamics simulations that directly show membrane binding to the concave face of N-BAR domains, resulting in the generation of local membrane curvature that matches the curvature presented by the BAR domain. These simulations provide direct molecular-scale evidence that BAR domains create curvature by acting as a scaffold, forcing the membrane to locally adopt the intrinsic shape of the BAR domain. We find that BAR domains bind strongly through the maximum curvature surface and, additionally, at an orientation that presents a lesser degree of curvature, thus enabling N-BAR domains to induce a range of local curvatures. Finally, we find that the N-terminal region may play a role in biasing the orientations of N-BAR domains on the membrane surface to those that favor binding to the concave face and subsequent membrane bending.
BAR（Bin/Amphiphysin/Rvs）结构域产生膜曲率的过程被认为涉及带负电荷的细胞膜与BAR结构域带正电荷的凹面的贴合。最近的研究工作[彼得，B.J.等人（2004年）《科学》，303卷，495 - 499页；增田，M.等人（2006年）《欧洲分子生物学组织杂志》，25卷，2889 - 2897页；以及盖洛普，J.L.等人（2006年）《欧洲分子生物学组织杂志》，25卷，2898 - 2910页]已经证明了带电荷的新月形表面以及N端两亲性螺旋（存在于N - BAR结构域中）对于产生膜曲率的重要性。这些实验表明，曲率是由嵌入脂质双层的N端螺旋和起“支架”作用以形成膜曲率的带电荷新月形二聚体的协同作用产生的。在此，我们展示了原子尺度的分子动力学模拟，其直接表明膜与N - BAR结构域的凹面结合，导致产生与BAR结构域呈现的曲率相匹配的局部膜曲率。这些模拟提供了直接的分子尺度证据，证明BAR结构域通过作为支架起作用来产生曲率，迫使膜局部采用BAR结构域的固有形状。我们发现BAR结构域通过最大曲率表面强烈结合，此外，还以呈现较小曲率程度的取向结合，从而使N - BAR结构域能够诱导一系列局部曲率。最后，我们发现N端区域可能在使N - BAR结构域在膜表面上的取向偏向于有利于与凹面结合及随后的膜弯曲的取向上发挥作用。
