Crystal structures of a polypeptide processing and secretion transporter
Crystal structures of a polypeptide processing and secretion transporter
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DOI：
10.1038/nature14623
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发表时间：
2015-07-23
期刊：
影响因子：
64.8
通讯作者：
Chen, Jue
中科院分区：
文献类型：
--
作者：
Lin, David Yin-wei;Huang, Shuo;Chen, Jue
细菌分泌肽和蛋白质进行交流，毒害竞争对手，操纵宿主细胞。在各种蛋白质转运机制中，含肽酶的ATP结合盒转运体（PCAT）是一种非常简单的蛋白质转运机制。每个PCAT含有两个切割底物分泌信号的肽酶结构域、两个形成易位途径的跨膜结构域和两个水解ATP的核苷酸结合结构域。在革兰氏阳性菌中，PCAT既作为成熟蛋白酶又作为群体感应或抗微生物多肽的输出者。在革兰氏阴性菌中，PCAT与其他两种膜蛋白相互作用形成1型分泌系统。在这里，我们提出了两种不同构象的热纤梭菌PCAT 1的晶体结构。这些结构，伴随着生化数据，表明易位途径是一个大的α-螺旋桶足以容纳小折叠蛋白质。ATP结合交替进入跨膜途径，也调节蛋白酶活性，从而将底物加工与易位偶联。
Bacteria secrete peptides and proteins to communicate, to poison competitors, and to manipulate host cells. Among the various protein-translocation machineries, the peptidase-containing ATP-binding cassette transporters (PCATs) are appealingly simple. Each PCAT contains two peptidase domains that cleave the secretion signal from the substrate, two transmembrane domains that form a translocation pathway, and two nucleotide-binding domains that hydrolyse ATP. In Gram-positive bacteria, PCATs function both as maturation proteases and exporters for quorum-sensing or antimicrobial polypeptides. In Gram-negative bacteria, PCATs interact with two other membrane proteins to form the type 1 secretion system. Here we present crystal structures of PCAT1 from Clostridium thermocellum in two different conformations. These structures, accompanied by biochemical data, show that the translocation pathway is a large a-helical barrel sufficient to accommodate small folded proteins. ATP binding alternates access to the transmembrane pathway and also regulates the protease activity, thereby coupling substrate processing to translocation.