Abstract
The translation initiation factor eIF4A is cleaved within mammalian cells infected by foot-and-mouth disease virus (FMDV). The FMDV 3C protease cleaves eIF4AI (between residues E143 and V144), but not the closely related eIF4AII. Modification of eIF4AI, to produce a sequence identical to eIF4AII around the cleavage site, blocked proteolysis. Alignment of mammalian eIF4AI onto the three-dimensional structure of yeast eIF4A located the scissile bond within an exposed, flexible portion of the molecule. The N- and C-terminal cleavage products of eIF4AI generated by FMDV 3C dissociate. Cleavage of eIF4AI by FMDV 3C is thus expected to inactivate it.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3C Viral Proteases
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Amino Acid Sequence
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Animals
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Binding Sites
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Cells, Cultured
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism*
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Eukaryotic Initiation Factor-4A
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Foot-and-Mouth Disease Virus / enzymology*
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Foot-and-Mouth Disease Virus / genetics
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Fungal Proteins / chemistry
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Humans
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Models, Molecular
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Molecular Sequence Data
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Peptide Initiation Factors / chemistry
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Peptide Initiation Factors / genetics
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Peptide Initiation Factors / metabolism*
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Peptide Mapping
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Protein Conformation
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Substrate Specificity
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Viral Proteins / genetics
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Viral Proteins / metabolism*
Substances
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Fungal Proteins
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Peptide Initiation Factors
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Recombinant Proteins
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Viral Proteins
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Eukaryotic Initiation Factor-4A
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Cysteine Endopeptidases
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3C Viral Proteases