The BAR-domain family of proteins: a case of bending and binding? The membrane bending and GTPase-binding functions of proteins from the BAR-domain family
The BAR-domain family of proteins: a case of bending and binding? The membrane bending and GTPase-binding functions of proteins from the BAR-domain family
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DOI：
10.1038/sj.embor.7400105
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发表时间：
2004-03-01
期刊：
影响因子：
7.7
通讯作者：
Habermann, B
中科院分区：
文献类型：
--
作者：
Habermann, B
最近，通过一份关于果蝇两栖动物蛋白中棒状结构域晶体结构的报告，杆状结构域成为科学研究的中心。虽然只在序列水平上弱保守，但BAR结构域的结构与Rho-和Arf-GTP酶的效应器Arfaptin 2的GTP酶结合域显示出惊人的相似性。根据这一序列和结构相似性，这两个蛋白质被归类为同一家族--杆域家族，它们可能也具有相似的功能特征。本文介绍了对两亲蛋白和Arfaptin 2的BAR结构域序列进行数据库搜索的结果。这一搜索发现了各种相关的蛋白质，其中大多数参与了细胞内运输，特别是内吞作用。例如，BAR结构域家族包括内啡肽、Centaurinbeta家族的GTP酶激活蛋白和寡聚精神蛋白，最近被证明与小GTPase Rab5相互作用的适配蛋白APPL1和APPL2，以及排序Nexin家族的成员。根据双体菌素和Arfaptin 2的结构以及双体菌素在内吞作用早期的细胞作用，BAR结构域的功能被定义为二聚化基序和感应膜弯曲的功能。然而，关于Arfaptin 2的数据以及现在关于接头蛋白APPL1和2的数据表明，bar结构域的另一个功能是与小的GTP酶结合。
BAR-domains recently took centre stage in science through a report on the crystal structure of this domain in Drosophila Amphiphysin. Though only weakly conserved at the sequence level, the structure of the BAR domain shows striking similarity to the GTPase-binding domain of Arfaptin 2, an effector of Rho- and Arf-GTPases. On the basis of this sequence and structural similarity, these two proteins have been classified as belonging to the same family, the BAR-domain family, and they probably also have similar functional characteristics. Presented here are the results of a database search for the sequence of the BAR domain of Amphiphysin and Arfaptin 2. This search identified a variety of related proteins, most of which are involved in intracellular transport and especially in endocytosis. For example, the BAR-domain family includes Endophilins, GTPase-activating proteins of the Centaurinbeta family and Oligophrenins, the adaptor proteins APPL1 and APPL2 that were recently shown to interact with the small GTPase Rab5, as well as members of the Sorting nexin family. On the basis of the structures of Amphiphysin and Arfaptin 2 and the cellular role of Amphiphysins in the early steps of endocytosis, the functions of the BAR domain have been defined as a dimerization motif and as sensing and inducing membrane curvature. However, data on Arfaptin 2 and now also on the Adaptor proteins APPL1 and 2 suggest that another function of the BAR domain is to bind to small GTPases.