Three structural solutions for bacterial adhesion pilus stability and superelasticity.
Three structural solutions for bacterial adhesion pilus stability and superelasticity.
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DOI：
10.1016/j.str.2023.03.005
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发表时间：
2023-05-04
期刊：
影响因子：
5.7
通讯作者：
Bullitt, Esther
中科院分区：
文献类型：
--
作者：
Doran, Matthew H.;Baker, Joseph L.;Dahlberg, Tobias;Andersson, Magnus;Bullitt, Esther
细菌粘附皮利是介导不同上皮环境中宿主-病原体相互作用的关键毒力因子。采用多模式方法，我们探讨了支撑源自肠致病性（ETEC）和尿路致病性（UPEC）细菌的皮利生物物理特性的结构基础。使用冷冻电子显微镜，我们解决了来自ETEC细菌的三种疫苗靶皮利的结构，CFA/I，CS 17和CS20。将这些和以前的菌毛结构与力谱和转向分子动力学模拟配对，我们发现亚基-亚基相互作用能和菌毛解旋所需的力之间存在很强的相关性，而不管遗传相似性如何。皮利整合了三种结构解决方案来稳定它们的组装：层与层的相互作用，N-末端与远端亚基的相互作用，以及来自相邻亚基的延伸环相互作用。调整这些结构的解决方案改变了生物物理性质的皮利，并促进超弹性行为，这是必不可少的持续细菌附着。许多细菌在被专门的细丝持续结合后引发疾病。这些“皮利”展开和重绕以减少细胞接触点处的力。正如Doran等人所证明的，皮利的解旋力主要取决于它们的结构，而不是菌毛蛋白的遗传密码。
Bacterial adhesion pili are key virulence factors that mediate host-pathogen interactions in diverse epithelial environments. Deploying a multimodal approach, we probed the structural basis underpinning the biophysical properties of pili originating from enterotoxigenic (ETEC) and uropathogenic (UPEC) bacteria. Using cryo-electron microscopy we solved the structures of three vaccine target pili from ETEC bacteria, CFA/I, CS17, and CS20. Pairing these and previous pilus structures with force spectroscopy and steered molecular dynamics simulations, we find a strong correlation between subunit-subunit interaction energies and the force required for pilus unwinding, irrespective of genetic similarity. Pili integrate three structural solutions for stabilizing their assemblies: layer-to-layer interactions, N-terminal interactions to distant subunits, and extended loop interactions from adjacent subunits. Tuning of these structural solutions alters the biophysical properties of pili and promotes the superelastic behaviour that is essential for sustained bacterial attachment. Many bacteria initiate disease after sustained binding by specialized filaments. These “pili” unwind and rewind to reduce the force at the point of cell contact. As demonstrated in Doran et al., pili depend primarily on their structure, rather than on the pilus proteins’ genetic code, for the unwinding force.
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影响因子：
64.5
作者：
Hospenthal MK;Redzej A;Dodson K;Ukleja M;Frenz B;Rodrigues C;Hultgren SJ;DiMaio F;Egelman EH;Waksman G
通讯作者：
Waksman G
DOI：
10.1016/j.str.2017.10.004
发表时间：
2017-12-05
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Hospenthal MK;Zyla D;Costa TRD;Redzej A;Giese C;Lillington J;Glockshuber R;Waksman G
通讯作者：
Waksman G
影响因子：
2.9
作者：
Krivov, Georgii G.;Shapovalov, Maxim V.;Dunbrack, Roland L., Jr.
通讯作者：
Dunbrack, Roland L., Jr.
影响因子：
3.9
作者：
Girardeau, JP;Bertin, Y;Callebaut, I
通讯作者：
Callebaut, I
影响因子：
3.6
作者：
Lee, Gwenyth;Paredes Olortegui, Maribel;Kosek, Margaret
通讯作者：
Kosek, Margaret