Structural and energetic basis of folded-protein transport by the FimD usher.

Structural and energetic basis of folded-protein transport by the FimD usher.
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DOI:
10.1038/nature12007
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发表时间:
2013-04-11
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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1型皮利是由尿路致病性大肠杆菌(UPEC)产生的多亚基纤维,在识别和粘附宿主组织中起关键作用。在菌毛生物发生期间,亚基被募集到外膜组装平台FimD引导器,其催化它们的聚合并介导菌毛分泌。最近的起始复合物的晶体结构提供了见解的菌毛生物发生的起始步骤,导致孔激活,但很少有人知道接下来的伸长步骤。为了解决这个问题,我们确定了延伸复合物的结构,其中FimD被由FimC:FimF:FimG:FimH组成的尖端复合物组装体穿过。该结构揭示了防止新生菌毛通过FimD孔回滑所需的构象变化,并且还揭示了引导孔的意想不到的性质。我们表明,引导孔是积极的设计,以促进孔内的基板通道和孔腔和折叠基板之间的圆形结合界面起着运输的作用,通过定义一个低能量的途径沿着引导新生菌毛聚合物在分泌过程中。
Type 1 pili, produced by uropathogenic Escherichia coli (UPEC), are multisubunit fibers that play crucial roles in recognition of and adhesion to host tissues. During pilus biogenesis, subunits are recruited to an outer membrane assembly platform, the FimD usher, which catalyzes their polymerization and mediates pilus secretion. The recent crystal structure of an initiation complex provided insights into the initiation step of pilus biogenesis resulting in pore activation, but very little is known about the elongation steps that follow. To address this question, we determined the structure of an elongation complex whereby FimD is traversed by the tip complex assembly composed of FimC:FimF:FimG:FimH. This structure reveals the conformational changes required to prevent backsliding of the nascent pilus through the FimD pore and also reveals unexpected properties of the usher pore. We show that the usher pore is energetically designed to facilitate substrate passage within the pore and that the circular binding interface between the pore lumen and the folded substrate plays a role in transport by defining a low energy pathway along which the nascent pilus polymer is guided during secretion.
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