Abstract
Vibrio cholerae RTX (repeats in toxin) is an actin-disrupting toxin that is autoprocessed by an internal cysteine protease domain (CPD). The RTX CPD is efficiently activated by the eukaryote-specific small molecule inositol hexakisphosphate (InsP6), and we present the 2.1 angstrom structure of the RTX CPD in complex with InsP6. InsP6 binds to a conserved basic cleft that is distant from the protease active site. Biochemical and kinetic analyses of CPD mutants indicate that InsP6 binding induces an allosteric switch that leads to the autoprocessing and intracellular release of toxin-effector domains.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyltransferases / chemistry*
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Acyltransferases / genetics
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Acyltransferases / metabolism*
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Allosteric Regulation
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Bacterial Toxins / chemistry*
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Bacterial Toxins / genetics
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Bacterial Toxins / metabolism*
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Binding Sites
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Catalytic Domain
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Crystallography, X-Ray
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Cysteine Endopeptidases / chemistry*
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism*
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Enzyme Activation
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism*
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Hydrogen Bonding
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Models, Molecular
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Phytic Acid / metabolism*
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Point Mutation
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Protein Structure, Secondary
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Surface Plasmon Resonance
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Vibrio cholerae / chemistry*
Substances
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Bacterial Proteins
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Bacterial Toxins
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Guanosine 5'-O-(3-Thiotriphosphate)
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Phytic Acid
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Acyltransferases
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RtxC protein, Vibrio cholerae
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Cysteine Endopeptidases