Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG.
Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG.
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DOI：
10.1038/nature13768
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发表时间：
2014-12-11
期刊：
影响因子：
64.8
通讯作者：
Remaut, Han
中科院分区：
文献类型：
--
作者：
Goyal, Parveen;Krasteva, Petya V.;Van Genven, Nani;Gubellini, Francesca;Van den Broeck, Imke;Troupiotis-Tsailaki, Anastassia;Jonckheere, Wim;Pehau-Arnaudet, Gerard;Pinkner, Jerome S.;Chapman, Matthew R.;Hultgren, Scott J.;Howorka, Stefan;Fronzes, Remi;Remaut, Han
卷曲是功能性淀粉样纤维，构成类杆菌和变形杆菌(主要是α和γ类)形成的膜生物膜细胞外基质的主要蛋白质成分。它们在致病菌株中具有适合性优势，并在菌血症期间诱导强烈的促炎反应。卷曲的形成需要专门的蛋白质分泌机制，包括外膜脂蛋白CsgG和两种可溶性辅助蛋白CsgE和CsgF。在这里，我们报告了大肠杆菌CsgG的非脂化、可溶形式以及其天然膜提取构象的X射线结构。CsgG形成一个由9个反密码子结合结构域样单位组成的寡聚运输复合体，这些单位形成一个36链的β桶，它穿过双层并连接到周质中的笼状前庭。跨膜结构域和周质结构域被0.9 nm的通道收缩隔开，该通道由三个堆叠的同心苯丙氨酸、天冬氨酸和酪氨酸环组成，可以引导延伸的多肽底物通过分泌孔。特异性因子CsgE形成一个非单体接头，结合并关闭分泌通道的周质表面，形成一个24,000ä3的预缩室。我们的结构、功能和电生理分析表明，CsgG是一种非门控、非选择性的蛋白质分泌通道，有望采用基于扩散的、熵驱动的运输机制。
Curli are functional amyloid fibres that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria (predominantly of the α and γ classes). They provide a fitness advantage in pathogenic strains and induce a strong pro-inflammatory response during bacteraemia. Curli formation requires a dedicated protein secretion machinery comprising the outer membrane lipoprotein CsgG and two soluble accessory proteins, CsgE and CsgF. Here we report the X-ray structure of Escherichia coli CsgG in a non-lipidated, soluble form as well as in its native membrane-extracted conformation. CsgG forms an oligomeric transport complex composed of nine anticodon-binding-domain-like units that give rise to a 36-stranded β-barrel that traverses the bilayer and is connected to a cage-like vestibule in the periplasm. The trans-membrane and periplasmic domains are separated by a 0.9-nm channel constriction composed of three stacked concentric phenylalanine, asparagine and tyrosine rings that may guide the extended polypeptide substrate through the secretion pore. The specificity factor CsgE forms a nonameric adaptor that binds and closes off the periplasmic face of the secretion channel, creating a 24,000 Å3 pre-constriction chamber. Our structural, functional and electrophysiological analyses imply that CsgG is an ungated, non-selective protein secretion channel that is expected to employ a diffusion-based, entropy-driven transport mechanism.
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影响因子：
2.9
作者：
Dueholm, Morten S.;Nielsen, Soren B.;Hein, Kim L.;Nissen, Poul;Chapman, Matthew;Christiansen, Gunna;Nielsen, Per Halkjaer;Otzen, Daniel E.
通讯作者：
Otzen, Daniel E.
影响因子：
3.7
作者：
Dueholm MS;Albertsen M;Otzen D;Nielsen PH
通讯作者：
Nielsen PH
影响因子：
82.9
作者：
Herwald, H;Mörgelin, M;Björck, L
通讯作者：
Björck, L
影响因子：
14.8
作者：
Cegelski, Lynette;Pinkner, Jerome S.;Hammer, Neal D.;Cusumano, Corinne K.;Hung, Chia S.;Chorell, Erik;Aberg, Veronica;Walker, Jennifer N.;Seed, Patrick C.;Almqvist, Fredrik;Chapman, Matthew R.;Hultgren, Scott J.
通讯作者：
Hultgren, Scott J.
DOI：
10.1107/s090744490903947x
发表时间：
2010-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Cowtan K
通讯作者：
Cowtan K