Calcium-Driven Folding of RTX Domain b-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F16%3A10326639" target="_blank" >RIV/00216208:11310/16:10326639 - isvavai.cz</a>
Výsledek na webu
<a href="http://www.sciencedirect.com/science/article/pii/S1097276516300016" target="_blank" >http://www.sciencedirect.com/science/article/pii/S1097276516300016</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.molcel.2016.03.018" target="_blank" >10.1016/j.molcel.2016.03.018</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Calcium-Driven Folding of RTX Domain b-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts
Popis výsledku v původním jazyce
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 β-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.
Název v anglickém jazyce
Calcium-Driven Folding of RTX Domain b-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts
Popis výsledku anglicky
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 β-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.
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
CE - Biochemie
OECD FORD obor
—
Návaznosti výsledku
Projekt
—
Návaznosti
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2016
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Molecular Cell
ISSN
1097-2765
e-ISSN
—
Svazek periodika
62
Číslo periodika v rámci svazku
1
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
17
Strana od-do
46-62
Kód UT WoS článku
000374119600007
EID výsledku v databázi Scopus
2-s2.0-84962446659