A general amphipathic α-helical motif for sensing membrane curvature
A general amphipathic α-helical motif for sensing membrane curvature
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DOI：
10.1038/nsmb1194
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发表时间：
2007-02-01
影响因子：
16.8
通讯作者：
Antonny, Bruno
中科院分区：
文献类型：
--
作者：
Drin, Guillaume;Casella, Jean-Francois;Antonny, Bruno
高尔基体相关蛋白ArfGAP 1具有不寻常的膜吸附两亲性α螺旋：其极面带弱电荷，主要含有丝氨酸和苏氨酸残基。我们表明，这一功能解释了特异性的ArfGAP 1弯曲与平坦的脂膜。我们建立了一个算法来识别蛋白质数据库中富含丝氨酸和苏氨酸残基的其他潜在的两亲性α-螺旋。在识别的序列中，我们发现三个作为膜曲率传感器。在golgin GMAP-210中，传感器可以用于在长的盘绕线圈的末端捕获小囊泡。在Osh 4p/Kes 1 p中，它在膜之间运输甾醇，传感器控制进入甾醇结合口袋。在核孔蛋白Nup 133中，传感器对应于β-螺旋桨结构的暴露环。因此，富含Ser/Thr的两亲性螺旋定义了各种功能的蛋白质用于感测膜曲率的一般基序。
The Golgi-associated protein ArfGAP1 has an unusual membrane-adsorbing amphipathic alpha-helix: its polar face is weakly charged, containing mainly serine and threonine residues. We show that this feature explains the specificity of ArfGAP1 for curved versus flat lipid membranes. We built an algorithm to identify other potential amphipathic alpha-helices rich in serine and threonine residues in protein databases. Among the identified sequences, we show that three act as membrane curvature sensors. In the golgin GMAP-210, the sensor may serve to trap small vesicles at the end of a long coiled coil. In Osh4p/Kes1p, which transports sterol between membranes, the sensor controls access to the sterol-binding pocket. In the nucleoporin Nup133, the sensor corresponds to an exposed loop of a beta-propeller structure. Ser/Thr-rich amphipathic helices thus define a general motif used by proteins of various functions for sensing membrane curvature.