title: Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site.
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.
authors.affiliation: School of Life Sciences, MSI/WTB Complex, University of Dundee, Dundee, UK.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Ross-Smith
authors.forename: C G
authors.initials: CG
authors.lastname: Proud
authors.forename: G J
authors.initials: GJ
authors.lastname: Belsham
mesh_terms: D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D039601:Eukaryotic Initiation Factor-4A; D029544:Foot-and-Mouth Disease Virus / Q000201:enzymology* / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010449:Peptide Mapping; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D010448:Peptide Initiation Factors; D011994:Recombinant Proteins; D014764:Viral Proteins; D039601:Eukaryotic Initiation Factor-4A; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases