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Poliovirus 2A proteinase cleaves directly the eIF‐4G subunit of eIF‐4F complex
Author(s) -
Ventoso Ivan,
MacMillan Susan E,
Hershey John W.B,
Carrasco Luis
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01027-8
Subject(s) - cleavage (geology) , maltose binding protein , coxsackievirus , poliovirus , initiation factor , protein subunit , picornaviridae , peptide , biology , chemistry , messenger rna , biochemistry , recombinant dna , virology , virus , translation (biology) , enterovirus , paleontology , fracture (geology) , gene , fusion protein
The initiation of translation on eukaryotic mRNA is governed by the concerted action of polypeptides of the eIF‐4F complex. One of these polypeptides, eIF‐4G, is proteolytically inactivated upon infection with several members of the Picornaviridae family. This cleavage occurs by the action of virus‐encoded proteinases: 2A pro (entero‐ and rhinovirus) or L pro (aphthovirus). An indirect mode of eIF‐4G cleavage through the activation of a second cellular proteinase has been proposed in the case of poliovirus. Although cleavage of eIF‐4G by rhino‐ and coxsackievirus 2A pro has been achieved directly in vitro, a similar activity has not been documented to date for poliovirus 2A pro . We report here that a recombinant form of poliovirus 2A pro fused to maltose binding protein (MBP) directly cleaves human eIF‐4G from a highly purified eIF‐4F complex. Efficient cleavage of eIF‐4G requires magnesium ions. The presence of other initiation factors such as eIF‐3, eIF‐4A or eIF‐4B mimics in part the stimulatory effect of magnesium ions and probably stabilizes the cleavage products of eIF‐4G generated by 2A pro . These results suggest that efficient cleavage of eIF‐4G by MBP‐2A pro requires a proper conformation of this factor. Finally, MBP‐2A pro protein cleaves an eIF‐4G‐derived synthetic peptide at the same site as rhino‐ and coxsackievirus 2A pro (R485‐G486).