Mechanism of endophilin N-BAR domain-mediated membrane curvature
Mechanism of endophilin N-BAR domain-mediated membrane curvature
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DOI：
10.1038/sj.emboj.7601174
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发表时间：
2006-06-21
期刊：
影响因子：
11.4
通讯作者：
T McMahon, Harvey
中科院分区：
文献类型：
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作者：
Gallop, Jennifer L.;Jao, Christine C.;T McMahon, Harvey
Endophilin-A1是一种富含于突触的BAR结构域蛋白，参与突触囊泡内吞作用。它通过C-末端SH 3结构域与发动蛋白和突触连接蛋白结合。我们研究BAR结构域和N-末端两亲性螺旋，膜结合后折叠，作为一个功能单元（N-BAR结构域），以促进二聚化和膜曲率产生的机制。通过电子顺磁共振光谱，我们表明，这两亲性螺旋是外围绑定在膜的平面，插入的中点对齐与磷酸盐水平的头基。这将螺旋放置在最佳位置以实现膜曲率生成。我们解决了大鼠endophilin-A1 BAR结构域的晶体结构，并检查了一个独特的插入突出的膜相互作用面。该插入物被预测形成另外的两亲性螺旋，并且对于曲率生成是重要的。它的存在定义了BAR结构域的内亲蛋白/那德林亚类。我们建议，N-BAR结构域的功能作为低亲和力二聚体调节结合伴侣招聘高膜曲率的地区。
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.