Membrane Binding by the Endophilin N-BAR Domain
Membrane Binding by the Endophilin N-BAR Domain
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DOI：
10.1016/j.bpj.2009.08.043
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发表时间：
2009-11-18
影响因子：
3.4
通讯作者：
Voth, Gregory A.
中科院分区：
文献类型：
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作者：
Cui, Haosheng;Ayton, Gary S.;Voth, Gregory A.
内亲素N末端两亲性螺旋Bin/两亲素/RVS同源(N-bar)结构域的结构是独特的，因为N-bar二聚体的弓形下有一个额外的插入螺旋。这一额外螺旋的结构在结晶学研究中尚未完全解决，因此对分子水平的分析提出了挑战。因此，使用大规模分子动力学模拟来研究单个亲内素N-bar与脂质双层之间的相互作用。在内嗜性N-bar的拱顶下的额外插入螺旋的各种可能的构型被建模，以检查它们对膜弯曲的影响。与电子顺磁共振谱类似的残基-残基和残基-脂质头基距离分析表明，插入螺旋在模拟过程中保持垂直于N-bar的长轴。还发现膜的弯曲程度与附加插入螺旋的取向直接相关，并且垂直构型产生的最大曲率与突变实验一致。此外，拱顶两个N-bar单体之间形成的角度对插入螺旋的方向很敏感。提出了膜传感-结合-弯曲机制来描述内亲素N-bar与膜的相互作用过程。
The structure of the endophilin N-terminal amphipathic helix Bin/Amphiphysin/Rvs-homology (N-BAR) domain is unique because of an additional insert helix under the arch of the N-BAR dimer. The structure of this additional helix has not been fully resolved in crystallographic studies, and thus presents a challenge to molecular-level analysis. Large-scale molecular-dynamics simulations were therefore employed to investigate the interaction of a single endophilin N-BAR with a lipid bilayer. Various possible configurations of the additional insert helix under the top of the arch of the endophilin N-BAR were modeled to examine their effect on membrane bending. A residue-residue and residue-lipid headgroup distance analysis, similar to that performed with electron paramagnetic resonance spectroscopy, revealed that the insert helix remains perpendicular to the long axis of the N-BAR over the duration of the simulations. It was also found that the degree of membrane bending is directly related to the orientation of the additional insert helix, and that the perpendicular configuration generates the largest curvature consistent with mutation experiments. In addition, the angle formed between the two N-BAR monomers at the top of the arch is sensitive to the orientation of the insert helices. A membrane sensing-binding-bending mechanism is proposed to describe the process of an endophilin N-BAR interaction with a membrane.