| Autor: |
Megan R. Brady, Fabiana San Martin, Garrett E. Debs, Kimberley H. Gibson, Azalia Rodríguez, Rosario Durán, Elsio A. Wunder, Albert I. Ko, Alejandro Buschiazzo, Charles V. Sindelar |
| Přispěvatelé: |
Yale University [New Haven], Molecular and structural microbiology / Microbiología Molecular y Estructural [Montevideo], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Yale School of Medicine [New Haven, Connecticut] (YSM), Analytical Biochemistry and Proteomics / Bioquímica y Proteómica Analíticas [Montevideo], Yale School of Public Health (YSPH), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Integrative Microbiology of Zoonotic Agents [Paris and Montevideo] (IMiZA), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur [Paris] (IP), This work was supported by National Institutes of Health grants R01 GM110530 (to C. V. S.), T32GM8283 (to M.R.B) and U01 AI 088752, R01 TW009504, R01 AI052473, R0 AI121207 (to A. K.)., Agencia Nacional de Investigacion e Innovacion grant FCE_3_2016_1_126797 and Agence Nationale de la Recherche grant ANR-18-CE15-0027-01 (to A. B). Cryo-EM data was collected at the Yale CryoEM Resource that is funded in part by the NIH grant 1S10OD023603-01A1., ANR-18-CE15-0027,LEPTOMOVE,Mécanismes moléculaires de la motilité chez les spirochètes: le modèle de l'endoflagelle des leptospires(2018) |
| Rok vydání: |
2022 |
| Předmět: |
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| DOI: |
10.1101/2022.03.03.482903 |
| Popis: |
Several Leptospira species are bacterial agents of leptospirosis, a neglected tropical disease responsible for ~1 million cases and 50,000 deaths each year worldwide. Leptospira, like other members of the Spirochaeta phylum, possess specially adapted flagella that remain confined within the periplasm. These appendages drive a unique, corkscrew-like swimming style that enables efficient motility and pathogenesis. However, the composition, function, and molecular architecture of spirochetal flagellar filaments remain poorly understood. We solved single-particle cryo-EM structures of isolated Leptospira flagellar filaments, comparing the wild-type form to two mutant forms with different missing components and abrogated motilities. The structures reveal a complex proteinaceous sheath surrounding a conserved core composed of the FlaB flagellin homolog. Sheath proteins were found to fall into two distinct categories, both of which are required for motility. Filament ‘coiling’ proteins, FcpA and FcpB, exert force on the filament when they bind its surface, causing the filament to stretch. In contrast, we identify sheath components FlaAP (newly discovered in this study) and FlaA2 as ‘template’ factors, which have little effect on filament shape by themselves, but partition the coiling proteins to one side of the filament. In this way, the two types of Leptospira sheath factors operate collectively on the flagellar filament to bend it from a ‘relaxed’ form associated with cell immobility, to a motility-competent shape that is tightly supercoiled. Our structures also indicate that core-sheath interactions are largely mediated by carbohydrate moieties from flagellin core side chain O-glycosylations. The supercoiling mechanism presented here provides a benchmark for studies with other bacteria, for which near-atomic resolution structures of flagellar filament in native supercoiled forms, are still lacking. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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