Department of Microbiology & Molecular Medicine and Geneva Center for Inflammation Research (GCIR), Faculty of Medicine, University of Geneva, Rue Michel Servet 1, 1211 Genève, Switzerland.
Cell Rep. 2023 Aug 29;42(8):112890. doi: 10.1016/j.celrep.2023.112890. Epub 2023 Jul 28.
Unidirectional growth of filamentous protein assemblies including the bacterial flagellum relies on dedicated polymerization factors (PFs). The molecular determinants and structural transitions imposed by PFs on multi-subunit assembly are poorly understood. Here, we unveil FlaY from the polarized α-proteobacterium Caulobacter crescentus as a defining member of an alternative class of specialized flagellin PFs. Unlike the paradigmatic FliD capping protein, FlaY relies on a funnel-like β-propeller fold for flagellin polymerization. FlaY binds flagellin and is secreted by the flagellar secretion apparatus, yet it can also promote flagellin polymerization exogenously when donated from flagellin-deficient cells, serving as a transferable, extracellular public good. While the surge in FlaY abundance precedes bulk flagellin synthesis, FlaY-independent filament assembly is enhanced by mutation of a conserved region in multiple flagellin paralogs. We suggest that FlaYs are (multi-)flagellin PFs that evolved convergently to FliDs yet appropriated the versatile β-propeller fold implicated in human diseases for chaperone-assisted filament assembly.
包括细菌鞭毛在内的丝状蛋白组装体的单向生长依赖于专门的聚合因子（PFs）。PFs 对多亚基组装施加的分子决定因素和结构转变知之甚少。在这里，我们揭示了来自极性 α-变形菌新月柄杆菌的 FlaY 是一类特殊的鞭毛蛋白 PF 的典型成员。与典型的 FliD 盖帽蛋白不同，FlaY 依赖于漏斗状的β-类 propeller 折叠来进行鞭毛蛋白聚合。FlaY 结合鞭毛蛋白并通过鞭毛分泌装置分泌，但当来自鞭毛缺陷细胞时，它也可以促进鞭毛蛋白的聚合，充当可转移的、细胞外的公共品。虽然 FlaY 丰度的激增先于大量鞭毛蛋白的合成，但突变多个鞭毛蛋白同源物中的保守区域可增强 FlaY 非依赖性的细丝组装。我们认为 FlaYs 是（多）鞭毛蛋白 PF，它们与 FliDs 趋同进化，但又采用了涉及人类疾病的多功能β-类 propeller 折叠来辅助纤维组装。
