Affiliation:
1. Department of Microbiology, State University of New York, Stony Brook 11794-8621.
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.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference49 articles.
1. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications;Bazan J. F.;Proc. Natl. Acad. Sci. USA,1988
2. Mapping the active site of papain with the aid of peptide substrates and inhibitors;Berger A.;Phil. Proc. R. Soc. London B,1970
3. Poliovirus mutant that does not selectively inhibit host cell protein synthesis;Bernstein H. D.;Mol. Cell. Biol.,1985
4. Molecular cloning and complete sequence determination of RNA genome of human rhinovirus type 14;Callahan P. L.;Proc. Natl. Acad. Sci. USA,1985
5. Translation of poliovirus RNA in vitro: detection of two different initiation sites;Celma M. L.;J. Mol. Biol.,1975
Cited by
76 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献