Amphipathic lipid packing sensor motifs: probing bilayer defects with hydrophobic residues.
Amphipathic lipid packing sensor motifs: probing bilayer defects with hydrophobic residues.
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DOI：
10.1016/j.bpj.2012.11.3837
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
S. Vanni;Lydie Vamparys;R. Gautier;G. Drin;C. Etchebest;P. Fuchs;B. Antonny
中科院分区：
文献类型：
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作者：
S. Vanni;Lydie Vamparys;R. Gautier;G. Drin;C. Etchebest;P. Fuchs;B. Antonny
感测膜曲率允许对发生在膜结合细胞器表面的复杂反应进行微调。最敏感的膜曲率传感器之一，两亲性脂质包装传感器（ALPS）基序，似乎不认识膜本身的曲面几何形状，而是认识到，在脂质包装中产生的膜弯曲的缺陷。在配套文件中，我们表明，这些缺陷可以通过在平面脂质双层中引入锥形脂质来模仿，与实验观察一致。在这里，我们使用分子动力学（MD）模拟来表征ALPS结合到这样的脂质双层。ALPS基序通过保守机制识别脂质包装缺陷：通过将疏水残基插入双层中预先形成的大包装缺陷中来驱动肽分配。这种插入只引起自由包装缺陷的统计分布的微小修改。当单不饱和脂质被饱和脂质取代时，ALPS插入受到严重阻碍，导致包装缺陷减少。我们认为ALPS基序对脂质包装缺陷的超敏性是由于沿着单调的ALPS序列重复使用疏水插入沿着。
Sensing membrane curvature allows fine-tuning of complex reactions that occur at the surface of membrane-bound organelles. One of the most sensitive membrane curvature sensors, the Amphipathic Lipid Packing Sensor (ALPS) motif, does not seem to recognize the curved surface geometry of membranes per se; rather, it recognizes defects in lipid packing that arise from membrane bending. In a companion paper, we show that these defects can be mimicked by introducing conical lipids in a flat lipid bilayer, in agreement with experimental observations. Here, we use molecular-dynamics (MD) simulations to characterize ALPS binding to such lipid bilayers. The ALPS motif recognizes lipid-packing defects by a conserved mechanism: peptide partitioning is driven by the insertion of hydrophobic residues into large packing defects that are preformed in the bilayer. This insertion induces only minor modifications in the statistical distribution of the free packing defects. ALPS insertion is severely hampered when monounsaturated lipids are replaced by saturated lipids, leading to a decrease in packing defects. We propose that the hypersensitivity of ALPS motifs to lipid packing defects results from the repetitive use of hydrophobic insertions along the monotonous ALPS sequence.