Structure and Dynamics of Helix-0 of the N-BAR Domain in Lipid Micelles and Bilayers
Structure and Dynamics of Helix-0 of the N-BAR Domain in Lipid Micelles and Bilayers
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DOI：
10.1529/biophysj.108.134155
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Balbach, Jochen
中科院分区：
文献类型：
--
作者：
Low, Christian;Weininger, Ulrich;Balbach, Jochen
Bin/亲 Amphiphysin/Rvs同源（BAR）结构域通过其带正电的凹面与带负电的膜结合，从而产生并感知膜曲率。N - BAR结构域包含一个N末端延伸部分（螺旋 - 0），据预测在与膜结合时会形成一个两亲性螺旋。我们测定了人Bin1/亲 Amphiphysin II BAR结构域的螺旋 - 0在十二烷基硫酸钠和十二烷基磷酸胆碱胶束中的核磁共振结构以及纳秒到皮秒的动力学。对这个由34个氨基酸组成的肽段进行的分子动力学模拟揭示了它与去污剂分子之间的静电和疏水相互作用，这些相互作用促使从第8 - 10位残基到C末端形成螺旋结构。胶束中的取向通过主链酰胺质子交换得到了实验证实。模拟和实验都表明N末端区域是无序的，并且该肽段弯曲以适应胶束形状。螺旋 - 0的缺失降低了BAR结构域对脂质体的管状化作用，而螺旋 - 0肽段本身具有融合活性。这些发现支持了BAR结构域使膜弯曲的模型，在该模型中螺旋 - 0增加了对膜的结合亲和力并增强了曲率的产生。
Bin/Amphiphysin/Rvs-homology (BAR) domains generate and sense membrane curvature by binding the negatively charged membrane to their positively charged concave surfaces. N-BAR domains contain an N-terminal extension (helix-0) predicted to form an amphipathic helix upon membrane binding. We determined the NMR structure and nano-to-picosecond dynamics of helix-0 of the human Bin1/Amphiphysin II BAR domain in sodium dodecyl sulfate and dodecylphosphocholine micelles. Molecular dynamics simulations of this 34-amino acid peptide revealed electrostatic and hydrophobic interactions with the detergent molecules that induce helical structure formation from residues 8-10 toward the C-terminus. The orientation in the micelles was experimentally confirmed by backbone amide proton exchange. The simulation and the experiment indicated that the N-terminal region is disordered, and the peptide curves to adopted the micelle shape. Deletion of helix-0 reduced tubulation of liposomes by the BAR domain, whereas the helix-0 peptide itself was fusogenic. These findings support models for membrane curving by BAR domains in which helix-0 increases the binding affinity to the membrane and enhances curvature generation.