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-Structure paper
タイトル | Calcium-Driven Folding of RTX Domain β-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts. |
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ジャーナル・号・ページ | Mol Cell, Vol. 62, Issue 1, Page 47-62, Year 2016 |
掲載日 | 2016年4月7日 |
著者 | 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 要旨 | 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. |
リンク | Mol Cell / PubMed:27058787 |
手法 | SAS (X-ray synchrotron) / X線回折 |
解像度 | 1.25 - 1.45 Å |
構造データ | SASDB74: SASDB84: PDB-5cvw: PDB-5cxl: |
化合物 | ChemComp-CA: ChemComp-EDO: ChemComp-GOL: ChemComp-MG: ChemComp-HOH: ChemComp-NO3: |
由来 |
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キーワード | TOXIN / ADENYLATE CYCLASE / RTX MOTIFS / CALCIUM BINDING |