Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate.

Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate.
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DOI:
10.1038/nature10109
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发表时间:
2011-06-02
期刊:
影响因子:
64.8
通讯作者:
Waksman, Gabriel
Waksman, Gabriel
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Phan, Gilles;Remaut, Han;Wang, Tao;Allen, William J.;Pirker, Katharina F.;Lebedev, Andrey;Henderson, Nadine S.;Geibel, Sebastian;Volkan, Ender;Yan, Jun;Kunze, Micha B. A.;Pinkner, Jerome S.;Ford, Bradley;Kay, Christopher W. M.;Li, Huilin;Hultgren, Scott J.;Thanassi, David G.;Waksman, Gabriel

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1型皮利是革兰氏阴性菌中广泛存在的一类粘附性多亚基纤维的原型代表。在菌毛组装过程中,亚基作为伴侣结合复合物停靠在引导器上,引导器催化它们的聚合并介导菌毛穿过外膜的移位。我们报告的晶体结构的全长FimD迎来绑定的FimC:FimH伴侣:粘附素复合物和未绑定形式的FimD易位结构域。FimD:FimC:FimH结构显示FimH插入FimD 24链β-桶易位通道内。FimC:FimH通过与FimD的两个C-末端周质结构域相互作用而保持在适当位置,这是通过电子顺磁共振光谱在溶液中确认的结合模式。为了容纳FimH,引导塞结构域从桶腔移位到周质,伴随着β-桶中的显著构象变化。FimD的N-末端结构域被观察到处于理想位置,以催化新募集的分子伴侣:亚基复合物的掺入。FimD:FimC:FimH结构提供了对菌毛亚基掺入周期的独特见解,并捕获了蛋白质转运蛋白分泌其同源底物的行为的第一个视图。
Type 1 pili are the archetypal representative of a widespread class of adhesive multisubunit fibres in Gram-negative bacteria. During pilus assembly, subunits dock as chaperone-bound complexes to an usher, which catalyzes their polymerization and mediates pilus translocation across the outer membrane. We report the crystal structure of the full-length FimD usher bound to the FimC:FimH chaperone:adhesin complex and that of the unbound form of the FimD translocation domain. The FimD:FimC:FimH structure shows FimH inserted inside the FimD 24-stranded β-barrel translocation channel. FimC:FimH is held in place through interactions with the two C-terminal periplasmic domains of FimD, a binding mode confirmed in solution by electron paramagnetic resonance spectroscopy. To accommodate FimH, the usher plug domain is displaced from the barrel lumen to the periplasm, concomitant with a dramatic conformational change in the β-barrel. The N-terminal domain of FimD is observed in an ideal position to catalyse incorporation of a newly recruited chaperone:subunit complex. The FimD:FimC:FimH structure provides unique insights into the pilus subunit incorporation cycle, and captures the first view of a protein transporter in the act of secreting its cognate substrate.
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