Pasqualato Sebastiano, Renault Louis, Cherfils Jacqueline
Laboratoire d'Enzymologie et Biochimie Structurales, UPR 9063 CNRS, 1 avenue de la Terrasse, 91198 Gif sur Yvette cedex, France.
EMBO Rep. 2002 Nov;3(11):1035-41. doi: 10.1093/embo-reports/kvf221.
Arf proteins are important regulators of cellular traffic and the founding members of an expanding family of homologous proteins and genomic sequences. They depart from other small GTP-binding proteins by a unique structural device, which we call the 'interswitch toggle', that implements front-back communication from the N-terminus to the nucleotide binding site. Here we define the sequence and structural determinants that propagate information across the protein and identify them in all of the Arf family proteins other than Arl6 and Arl4/Arl7. The positions of these determinants lead us to propose that Arf family members with the interswitch toggle device are activated by a bipartite mechanism acting on opposite sides of the protein. The presence of this communication device might provide a more useful basis for unifying Arf homologs as a family than do the cellular functions of these proteins, which are mostly unrelated. We review available genomic sequences and functional data from this perspective, and identify a novel subfamily that we call Arl8.
Arf蛋白是细胞运输的重要调节因子，也是一个不断扩大的同源蛋白和基因组序列家族的创始成员。它们通过一种独特的结构机制与其他小GTP结合蛋白不同，我们称之为“开关间切换”，该机制实现了从N端到核苷酸结合位点的前后通信。在这里，我们定义了在整个蛋白质中传播信息的序列和结构决定因素，并在除Arl6和Arl4/Arl7之外的所有Arf家族蛋白中识别出它们。这些决定因素的位置使我们提出，具有开关间切换装置的Arf家族成员是通过作用于蛋白质相对两侧的二分机制激活的。与这些蛋白质大多不相关的细胞功能相比，这种通信装置的存在可能为将Arf同源物统一为一个家族提供更有用的基础。我们从这个角度回顾了可用的基因组序列和功能数据，并鉴定出一个我们称为Arl8的新亚家族。
