3O44

Crystal Structure of the Vibrio cholerae Cytolysin (HlyA) Heptameric Pore

Summary for 3O44

• Entry DOI: 10.2210/pdb3o44/pdb
• Related: 1XEZ
• Descriptor: Hemolysin (2 entities in total)
• Functional Keywords: pore-forming toxin, hemolysin, cytolysin, beta-barrel, channel, membrane protein, detergent-solubilized, liposome, toxin
• Biological source: Vibrio cholerae 12129(1)
• Total number of polymer chains: 14
• Total formula weight: 920097.39

Authors

De, S.,Olson, R. (deposition date: 2010-07-26, release date: 2011-04-20, Last modification date: 2024-11-06)

Primary citation

De, S.,Olson, R.
Crystal structure of the Vibrio cholerae cytolysin heptamer reveals common features among disparate pore-forming toxins.
Proc.Natl.Acad.Sci.USA, 108:7385-7390, 2011

PubMed Abstract: Pore-forming toxins (PFTs) are potent cytolytic agents secreted by pathogenic bacteria that protect microbes against the cell-mediated immune system (by targeting phagocytic cells), disrupt epithelial barriers, and liberate materials necessary to sustain growth and colonization. Produced by gram-positive and gram-negative bacteria alike, PFTs are released as water-soluble monomeric or dimeric species, bind specifically to target membranes, and assemble transmembrane channels leading to cell damage and/or lysis. Structural and biophysical analyses of individual steps in the assembly pathway are essential to fully understanding the dynamic process of channel formation. To work toward this goal, we solved by X-ray diffraction the 2.9-Å structure of the 450-kDa heptameric Vibrio cholerae cytolysin (VCC) toxin purified and crystallized in the presence of detergent. This structure, together with our previously determined 2.3-Å structure of the VCC water-soluble monomer, reveals in detail the architectural changes that occur within the channel region and accessory lectin domains during pore formation including substantial rearrangements of hydrogen-bonding networks in the pore-forming amphipathic loops. Interestingly, a ring of tryptophan residues forms the narrowest constriction in the transmembrane channel reminiscent of the phenylalanine clamp identified in anthrax protective antigen [Krantz BA, et al. (2005) Science 309:777-781]. Our work provides an example of a β-barrel PFT (β-PFT) for which soluble and assembled structures are available at high-resolution, providing a template for investigating intermediate steps in assembly.

PubMed: 21502531
DOI: 10.1073/pnas.1017442108

Experimental method

X-RAY DIFFRACTION (2.88 Å)