Catalysis of poliovirus VP0 maturation cleavage is not mediated by serine 10 of VP2.
The maturation of the poliovirus capsid occurs as the result of a single unexplained proteolytic event during which 58 to 59 copies of the 60 VP0 capsid protein precursors are cleaved. An autocatalytic mechanism for cleavage of VP0 to VP4 and VP2 was proposed by Arnold et al. (E. Arnold, M. Luo, G. Vriend, M. G. Rossman, A. C. Palmenberg, G. D. Parks, M. J. Nicklin, and E. Wimmer, Proc. Natl. Acad. Sci. USA 84:21-25, 1987) in which serine 10 of VP2 is activated by virion RNA to catalyze VP4-VP2 processing. The hypothesis rests on the observation that a hydrogen bond was observed between serine 10 of VP2 (S2010) and the carboxyl terminus of VP4 in three mature picornaviral atomic structures: rhinovirus 14, mengovirus, and poliovirus type 1 (Mahoney). We constructed mutant viruses with cysteine (S2010C) or alanine (S2010A) replacing serine 10 of VP2; these exhibited normal proteolytic processing of VP0. While our results do not exclude an autocatalytic mechanism for the maturation cleavage, they do eliminate the conserved S2010 residue as the catalytic amino acid.
Harber
J J
JJ
Department of Microbiology, State University of New York, Stony Brook 11794.
Bradley
J
J
Anderson
C W
CW
Wimmer
E
E
D000595:Amino Acid Sequence; D001483:Base Sequence; D002213:Capsid / Q000235:genetics* / Q000378:metabolism; D036022:Capsid Proteins; D003062:Codon / Q000235:genetics; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015345:Oligonucleotide Probes; D017955:Poliovirus / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011487:Protein Conformation; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D012694:Serine; D014771:Virion / Q000235:genetics
D036022:Capsid Proteins; D003062:Codon; D015345:Oligonucleotide Probes; D012367:RNA, Viral; C442541:VP2 protein, Poliovirus; C442544:VP2 protein, Rhinovirus; D012694:Serine