title: Determinants of substrate recognition by poliovirus 2A proteinase.
abstract: Poliovirus proteinase 2A (2Apro) is autocatalytically released from the viral polyprotein by cleavage in cis of a Tyr-Gly dipeptide at its own amino terminus, resulting in separation of the P1 structural and P2-P3 nonstructural protein precursors. A second Ty-Gly dipeptide within 3D polymerase is cleaved by 2Apro in trans, but this is not essential for viral proliferation. The mechanism which limits cleavage to only 2 of the 10 Tyr-Gly dipeptides within the poliovirus polyprotein has not been characterized. We have therefore undertaken a systematic mutational analysis of the VP1-2A site to elucidate determinants of substrate recognition by 2Apro. The P2 and P1' positions are important determinants for cis cleavage of this site, whereas a variety of substituents could be tolerated at the P2', P1, and P3 positions. The requirements for trans cleavage of this site were more stringent. We found that the 2Apro of coxsackievirus type A21 and rhinoviruses 2 and 14 have stringent requirements similar to those of poliovirus 2Apro for cleavage in trans.
authors.affiliation: Department of Microbiology, State University of New York, Stony Brook 11794-8621.
authors.forename: C U
authors.initials: CU
authors.lastname: Hellen
authors.forename: C K
authors.initials: CK
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Wimmer
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004151:Dipeptides / Q000378:metabolism; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014764:Viral Proteins
chemical_list: D004151:Dipeptides; D011498:Protein Precursors; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus