Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature.
Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature.
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DOI：
10.1038/s41598-017-06334-5
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发表时间：
2017-07-28
影响因子：
4.6
通讯作者：
Kitao A
中科院分区：
文献类型：
--
作者：
Takemura K;Hanawa-Suetsugu K;Suetsugu S;Kitao A
BAR 结构域超家族蛋白感知或诱导膜的弯曲。反 BAR 结构域 (I-BAR) 是形成直线“齐柏林飞艇形”二聚体的 BAR 结构域。本文通过全原子分子动力学模拟 (MD)、结合能分析以及 HeLa 细胞丝状伪足突变实验的影响，研究了 IRSp53 I-BAR 与脂质膜结合并使脂质膜变形的机制。 I-BAR在结晶时采用弯曲结构，但在MD上采用更平坦的形状。 I-BAR 与膜的结合通过约 30 个盐桥得以稳定，这与表明界面残基的点突变对结合亲和力影响很小的实验一致，而多个突变则具有相当大的影响。盐桥的形成增加了脂质的局部密度并使膜变形为凹形。此外，破坏 I-BAR 内关键分子内盐桥的点突变会降低结合亲和力；通过在 HeLa 细胞中表达这些突变体并观察它们的效果证实了这一点。结果表明，尽管 I-BAR 并不充当完全刚性的模板，但 I-BAR 的刚度对于膜变形很重要。
The BAR domain superfamily proteins sense or induce curvature in membranes. The inverse-BAR domain (I-BAR) is a BAR domain that forms a straight “zeppelin-shaped” dimer. The mechanisms by which IRSp53 I-BAR binds to and deforms a lipid membrane are investigated here by all-atom molecular dynamics simulation (MD), binding energy analysis, and the effects of mutation experiments on filopodia on HeLa cells. I-BAR adopts a curved structure when crystallized, but adopts a flatter shape in MD. The binding of I-BAR to membrane was stabilized by ~30 salt bridges, consistent with experiments showing that point mutations of the interface residues have little effect on the binding affinity whereas multiple mutations have considerable effect. Salt bridge formation increases the local density of lipids and deforms the membrane into a concave shape. In addition, the point mutations that break key intra-molecular salt bridges within I-BAR reduce the binding affinity; this was confirmed by expressing these mutants in HeLa cells and observing their effects. The results indicate that the stiffness of I-BAR is important for membrane deformation, although I-BAR does not act as a completely rigid template.
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影响因子：
5.3
作者：
Abbott, MA;Wells, DG;Fallon, JR
通讯作者：
Fallon, JR
DOI：
10.1083/jcb.152.3.579
发表时间：
2001-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Govind S;Kozma R;Monfries C;Lim L;Ahmed S
通讯作者：
Ahmed S
影响因子：
8
作者：
Liu, P-S;Jong, T-H;Leu, T-H
通讯作者：
Leu, T-H
影响因子：
5.5
作者：
KARPLUS, M;KUSHICK, JN
通讯作者：
KUSHICK, JN
影响因子：
3.4
作者：
Cui, Haosheng;Ayton, Gary S.;Voth, Gregory A.
通讯作者：
Voth, Gregory A.