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TitleCalcium-Driven Folding of RTX Domain β-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts.
Journal, issue, pagesMol Cell, Vol. 62, Issue 1, Page 47-62, Year 2016
Publish dateApr 7, 2016
AuthorsLadislav Bumba / Jiri Masin / Pavel Macek / Tomas Wald / Lucia Motlova / Ilona Bibova / Nela Klimova / Lucie Bednarova / Vaclav Veverka / Michael Kachala / Dmitri I Svergun / Cyril Barinka / Peter Sebo /
PubMed AbstractCalcium-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, ...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.
External linksMol Cell / PubMed:27058787
MethodsSAS (X-ray synchrotron) / X-ray diffraction
Resolution1.25 - 1.45 Å
Structure data

SASDB74:
CyaA Block I-V (Adenylate cyclase toxin Block I-V)
Method: SAXS/SANS

SASDB84:
CyaA Block V (Adenylate cyclase toxin Block V)
Method: SAXS/SANS

PDB-5cvw:
CRYSTAL STRUCTURE OF RTX DOMAIN BLOCK V OF ADENYLATE CYCLASE TOXIN FROM BORDETELLA PERTUSSIS
Method: X-RAY DIFFRACTION / Resolution: 1.25 Å

PDB-5cxl:
CRYSTAL STRUCTURE OF RTX DOMAIN BLOCK V OF ADENYLATE CYCLASE TOXIN FROM BORDETELLA PERTUSSIS
Method: X-RAY DIFFRACTION / Resolution: 1.45 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-GOL:
GLYCEROL / Glycerol

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER / Water

ChemComp-NO3:
NITRATE ION / Nitrate

Source
  • Bordetella pertussis (bacteria)
  • bordetella pertussis (strain atcc 9797 / dsm 5571 / nctc 10739 / 18323) (bacteria)
  • bordetella pertussis (strain tohama i / atcc baa-589 / nctc 13251) (bacteria)
KeywordsTOXIN / ADENYLATE CYCLASE / RTX MOTIFS / CALCIUM BINDING

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