Calcium-Driven Folding of RTX Domain ß-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts.
Mol Cell
; 62(1): 47-62, 2016 Apr 07.
Article
en En
| MEDLINE
| ID: mdl-27058787
ABSTRACT
Calcium-binding RTX proteins are equipped with C-terminal secretion signals and translocate from the Ca(2+)-depleted cytosol of Gram-negative bacteria directly into the Ca(2+)-rich external milieu, passing through the "channel-tunnel" ducts of type I secretion systems (T1SSs). Using Bordetella pertussis adenylate cyclase toxin, we solved the structure of an essential C-terminal assembly that caps the RTX domains of RTX family leukotoxins. This is shown to scaffold directional Ca(2+)-dependent folding of the carboxy-proximal RTX repeat blocks into ß-rolls. The resulting intramolecular Brownian ratchets then prevent backsliding of translocating RTX proteins in the T1SS conduits and thereby accelerate excretion of very large RTX leukotoxins from bacterial cells by a vectorial "push-ratchet" mechanism. Successive Ca(2+)-dependent and cosecretional acquisition of a functional RTX toxin structure in the course of T1SS-mediated translocation, through RTX domain folding from the C-terminal cap toward the N terminus, sets a paradigm that opens for design of virulence inhibitors of major pathogens.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Toxinas Bacterianas
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Calcio
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Sistemas de Secreción Tipo I
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Bacterias Gramnegativas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2016
Tipo del documento:
Article