Laboratoire de Chimie Bactérienne, UMR 7283 CNRS/Aix-Marseille Université, Institut de Microbiologie de la Méditerranée, Marseille, France.
Microbiology (Reading). 2023 Mar;169(3). doi: 10.1099/mic.0.001311.
Type 4 filaments (T4F) are a superfamily of filamentous nanomachines - virtually ubiquitous in prokaryotes and functionally versatile - of which type 4 pili (T4P) are the defining member. T4F are polymers of type 4 pilins, assembled by conserved multi-protein machineries. They have long been an important topic for research because they are key virulence factors in numerous bacterial pathogens. Our poor understanding of the molecular mechanisms of T4F assembly is a serious hindrance to the design of anti-T4F therapeutics. This review attempts to shed light on the fundamental mechanistic principles at play in T4F assembly by focusing on similarities rather than differences between several (mostly bacterial) T4F. This holistic approach, complemented by the revolutionary ability of artificial intelligence to predict protein structures, led to an intriguing mechanistic model of T4F assembly.
4 型纤维(T4F)是丝状纳米机器的超家族 - 在原核生物中几乎无处不在,功能多样 - 其中 4 型菌毛(T4P)是其定义成员。T4F 是由保守的多蛋白机器组装而成的 4 型菌毛聚合物。由于它们是许多细菌病原体中重要的毒力因子,因此长期以来一直是研究的重要课题。我们对 T4F 组装的分子机制的理解很差,这严重阻碍了抗 T4F 治疗药物的设计。本综述试图通过关注几种(主要是细菌)T4F 之间的相似之处而不是差异,阐明 T4F 组装中发挥作用的基本机制原理。这种整体方法,辅之以人工智能预测蛋白质结构的革命性能力,导致了 T4F 组装的一个有趣的机制模型。