Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms
Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms
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DOI：
10.1038/sj.emboj.7601176
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发表时间：
2006-06-21
期刊：
影响因子：
11.4
通讯作者：
Mochizuki, Naoki
中科院分区：
文献类型：
--
作者：
Masuda, Michitaka;Takeda, Soichi;Mochizuki, Naoki
新月形的条状(Bin/AmphiPhyin/RVS-Homology)结构域二聚体是一个多功能的蛋白质模块，可以感知和产生正膜曲率。人内亲和素-A1的杆状结构域二聚体，在3.1埃下溶解，具有一种独特的结构，由一对从新月形萌发出来的螺旋环状附件组成。附肢的短螺旋形成了一个疏水的脊线，横跨其中心的凹面。用纯化的bar结构域及其突变体在体外检测脂质体的结合和微管形成，结果表明该突起能穿透膜双层并增强脂质体的微管形成。在体内，表达BAR结构域的细胞表现出明显的质膜微管。此外，摆臂突变体失去了脂质体的管状活性，但仍保留了脂质体的结合。这些数据表明，刚性新月状二聚体的形状对管状结构至关重要。我们认为，除了通过氨基末端两亲性螺旋与膜结合外，棒结构域还通过新月的支架机构和脊膜的插入的协调作用来驱动膜的曲率。
The crescent-shaped BAR ( Bin/Amphiphysin/Rvs-homology) domain dimer is a versatile protein module that senses and generates positive membrane curvature. The BAR domain dimer of human endophilin-A1, solved at 3.1 angstrom, has a unique structure consisting of a pair of helix-loop appendages sprouting out from the crescent. The appendage's short helices form a hydrophobic ridge, which runs across the concave surface at its center. Examining liposome binding and tubulation in vitro using purified BAR domain and its mutants indicated that the ridge penetrates into the membrane bilayer and enhances liposome tubulation. BAR domain-expressing cells exhibited marked plasma membrane tubulation in vivo. Furthermore, a swinging-arm mutant lost liposome tubulation activity yet retaining liposome binding. These data suggested that the rigid crescent dimer shape is crucial for the tubulation. We here propose that the BAR domain drives membrane curvature by coordinate action of the crescent's scaffold mechanism and the ridge's membrane insertion in addition to membrane binding via amino-terminal amphipathic helix.