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Title | Calcium-Driven Folding of RTX Domain β-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts. |
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Journal, issue, pages | Mol Cell, Vol. 62, Issue 1, Page 47-62, Year 2016 |
Publish date | Apr 7, 2016 |
![]() | Ladislav 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 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, ...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. |
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Methods | SAS (X-ray synchrotron) / X-ray diffraction |
Resolution | 1.25 - 1.45 Å |
Structure data | ![]() SASDB74: ![]() SASDB84: ![]() PDB-5cvw: ![]() PDB-5cxl: |
Chemicals | ![]() ChemComp-CA: ![]() ChemComp-EDO: ![]() ChemComp-GOL: ![]() ChemComp-MG: ![]() ChemComp-HOH: ![]() ChemComp-NO3: |
Source |
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![]() | TOXIN / ADENYLATE CYCLASE / RTX MOTIFS / CALCIUM BINDING |