5CVW

CRYSTAL STRUCTURE OF RTX DOMAIN BLOCK V OF ADENYLATE CYCLASE TOXIN FROM BORDETELLA PERTUSSIS

Summary for 5CVW

• Entry DOI: 10.2210/pdb5cvw/pdb
• Descriptor: Bifunctional hemolysin/adenylate cyclase, CALCIUM ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: adenylate cyclase, rtx motifs, calcium binding, toxin
• Biological source: Bordetella pertussis (strain ATCC 9797 / DSM 5571 / NCTC 10739 / 18323)
• Cellular location: Secreted : J7QLC0
• Total number of polymer chains: 1
• Total formula weight: 16733.70

Authors

Motlova, L.,Barinka, C.,Bumba, L. (deposition date: 2015-07-27, release date: 2015-09-09, Last modification date: 2024-01-10)

Primary citation

Bumba, L.,Masin, J.,Macek, P.,Wald, T.,Motlova, L.,Bibova, I.,Klimova, N.,Bednarova, L.,Veverka, V.,Kachala, M.,Svergun, D.I.,Barinka, C.,Sebo, P.
Calcium-Driven Folding of RTX Domain beta-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts.
Mol.Cell, 62:47-62, 2016

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, 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.

PubMed: 27058787
DOI: 10.1016/j.molcel.2016.03.018

Experimental method

X-RAY DIFFRACTION (1.25 Å)