Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site

The translation initiation factor eIF4A is cleaved within mammalian cells i nfected by foot-and-mouth disease virus (FMDV). The FMDV 3C protease cleave s eIF4AI (between residues E143 and V144), but not the closely related eIF4 AII. Modification of eIF4AI, to produce a sequence identical to eIF4AII aro und the cleavage site, blocked proteolysis. Alignment of mammalian eIF4AI o nto the three-dimensional structure of yeast eIF4A located the scissile bon d within an exposed, flexible portion of the molecule. The N- and C-termina l cleavage products of eIF4AI generated by FMDV 3C dissociate. Cleavage of eIF4AI by FMDV 3C is thus expected to inactivate it. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rig hts reserved.