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首页> 外文期刊>EMBO Journal >Mechanism of endophilin N-BAR domain-mediated membrane curvature
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Mechanism of endophilin N-BAR domain-mediated membrane curvature

机译:机制endophilin N-BAR domain-mediated膜曲率

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摘要

Endophilin-A1 is a BAR domain-containing protein enriched at synapses and is implicated in synaptic vesicle endocytosis. It binds to dynamin and synaptojanin via a C-terminal SH3 domain. We examine the mechanism by which the BAR domain and an N-terminal amphipathic helix, which folds upon membrane binding, work as a functional unit (the N-BAR domain) to promote dimerisation and membrane curvature generation. By electron paramagnetic resonance spectroscopy, we show that this amphipathic helix is peripherally bound in the plane of the membrane, with the midpoint of insertion aligned with the phosphate level of headgroups. This places the helix in an optimal position to effect membrane curvature generation. We solved the crystal structure of rat endophilin-A1 BAR domain and examined a distinctive insert protruding from the membrane interaction face. This insert is predicted to form an additional amphipathic helix and is important for curvature generation. Its presence defines an endophilin/nadrin subclass of BAR domains. We propose that N-BAR domains function as low-affinity dimers regulating binding partner recruitment to areas of high membrane curvature.
机译:Endophilin-A1 domain-containing蛋白是一个酒吧在突触丰富,涉及突触囊泡内吞作用。并通过c端synaptojanin SH3域。域和检查机制的酒吧一个氨基端两亲的螺旋,折叠膜结合,作为一个功能单位(工作促进二聚和N-BAR域)膜曲率的一代。顺磁共振光谱,我们证明这种两亲的螺旋是外围地绑定飞机的膜,的中点插入与磷酸盐水平保持一致headgroups。位置效应膜曲率的一代。我们解决了老鼠的晶体结构endophilin-A1酒吧域和检查独特的插入的膜交互的脸。形成一个额外的两性分子的螺旋和重要的曲率的一代。定义了一个endophilin / nadrin子类的酒吧域。作为低亲和力二聚体调节约束力的合作伙伴招聘领域的高膜曲率。

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