Abstract
Mycobacterium tuberculosis uses the ESX-1/Snm system [early secreted antigen 6 kilodaltons (ESAT-6) system 1/secretion in mycobacteria] to deliver virulence factors into host macrophages during infection. Despite its essential role in virulence, the mechanism of ESX-1 secretion is unclear. We found that the unstructured C terminus of the CFP-10 substrate was recognized by Rv3871, a cytosolic component of the ESX-1 system that itself interacts with the membrane protein Rv3870. Point mutations in the signal that abolished binding of CFP-10 to Rv3871 prevented secretion of the CFP-10 (culture filtrate protein, 10 kilodaltons)/ESAT-6 virulence factor complex. Attachment of the signal to yeast ubiquitin was sufficient for secretion from M. tuberculosis cells, demonstrating that this ESX-1 signal is portable.
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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Amino Acid Sequence
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Antigens, Bacterial / chemistry
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Antigens, Bacterial / metabolism*
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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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Dimerization
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Membrane Proteins / metabolism
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Models, Biological
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Molecular Sequence Data
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Mutation
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / metabolism*
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Mycobacterium tuberculosis / pathogenicity
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Protein Binding
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Protein Sorting Signals*
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Protein Structure, Tertiary
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Protein Transport
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Recombinant Fusion Proteins / metabolism
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Two-Hybrid System Techniques
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Ubiquitin / metabolism
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Virulence Factors / chemistry
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Virulence Factors / metabolism*
Substances
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Antigens, Bacterial
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Bacterial Proteins
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CFP-10 protein, Mycobacterium tuberculosis
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ESAT-6 protein, Mycobacterium tuberculosis
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Membrane Proteins
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Protein Sorting Signals
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Recombinant Fusion Proteins
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Ubiquitin
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Virulence Factors