AI Article Synopsis
Article Abstract
The 2A proteinase (2A(pro)) of human rhinoviruses (HRVs) is a cysteine protease containing a structurally important zinc ion. In the viral polyprotein, the enzyme cleaves between the C terminus of VP1 and its own N terminus. 2A(pro) also processes the two isoforms of the cellular protein, eukaryotic initiation factor 4G (eIF4G). We have shown that mature HRV2 2A(pro), when translated in vitro in rabbit reticulocyte lysates, efficiently cleaves eIF4GI, although the enzyme was not immediately active upon synthesis. Here, we examine the relationship between self-processing and eIF4GI cleavage. The onset of both reactions first occurred at least 10 min after initiation of protein synthesis. Furthermore, when self-processing was prevented by a specific mutation between VP1 and 2A(pro), the VP1-2A(pro) precursor was essentially unable to cleave eIF4GI, implying that self-processing is a prerequisite for eIF4GI cleavage. 2A(pro) synthesized in the presence of a potent zinc chelator is inactive; however, upon addition of excess zinc, HRV2 2A(pro) rapidly gained activity. Finally, the presence of the zinc chelator in the culture medium can protect HeLa cells from HRV infection.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC152162 | PMC |
| http://dx.doi.org/10.1128/jvi.77.8.5021-5025.2003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interaction of 2A proteinase of human rhinovirus genetic group A with eIF4E is required for eIF4G cleavage during infection.
Virology
November 2017
Max F. Perutz Laboratories, Medical University of Vienna, Dept. of Medical Biochemistry, Vienna Biocenter, Dr. Bohr-Gasse 9/3, A-1030 Vienna, Austria. Electronic address:
In enteroviruses, the inhibition of protein synthesis from capped host cell mRNA is catalyzed by the virally encoded 2A proteinase (2A), which cleaves eukaryotic initiation factors (eIF) 4GI and 4GII. Despite much investigation, the exact mechanism of 2A cleavage remains however unclear. Here, we identify the domains responsible for the eIF4E/HRV2 2A interaction using molecular modelling and describe mutations that impair this interaction and delay in vitro cleavage of eIF4G isoforms.
View Article and Find Full Text PDFNMR analysis of the interaction of picornaviral proteinases Lb and 2A with their substrate eukaryotic initiation factor 4GII.
Protein Sci
December 2015
Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, Vienna, A-1030, Austria.
Messenger RNA is recruited to the eukaryotic ribosome by a complex including the eukaryotic initiation factor (eIF) 4E (the cap-binding protein), the scaffold protein eIF4G and the RNA helicase eIF4A. To shut-off host-cell protein synthesis, eIF4G is cleaved during picornaviral infection by a virally encoded proteinase; the structural basis of this reaction and its stimulation by eIF4E is unclear. We have structurally and biochemically investigated the interaction of purified foot-and-mouth disease virus (FMDV) leader proteinase (Lb(pro)), human rhinovirus 2 (HRV2) 2A proteinase (2A(pro)) and coxsackievirus B4 (CVB4) 2A(pro) with purified eIF4GII, eIF4E and the eIF4GII/eIF4E complex.
View Article and Find Full Text PDFCrystal structure of 2A proteinase from hand, foot and mouth disease virus.
J Mol Biol
November 2013
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 9 Dong Dan San Tiao, Beijing 100730, People's Republic of China.
EV71 is responsible for several epidemics worldwide; however, the effective antiviral drug is unavailable to date. The 2A proteinase (2A(pro)) of EV71 presents a promising drug target due to its multiple roles in virus replication, inhibition of host protein synthesis and evasion of innate immunity. We determined the crystal structure of EV71 2A(pro) at 1.
View Article and Find Full Text PDFSpecificity of human rhinovirus 2A(pro) is determined by combined spatial properties of four cleavage site residues.
J Gen Virol
July 2013
Max F. Perutz Laboratories, Medical University of Vienna, Dr. Bohr-Gasse 9/3, A-1030 Vienna, Austria.
The 2A proteinase (2A(pro)) of human rhinoviruses cleaves the virally encoded polyprotein between the C terminus of VP1 and its own N terminus. Poor understanding of the 2A(pro) substrate specificity of this enzyme has hampered progress in developing inhibitors that may serve as antiviral agents. We show here that the 2A(pro) of human rhinovirus (HRV) 1A and 2 (rhinoviruses from genetic group A) cannot self-process at the HRV14 (a genetic group B rhinovirus) cleavage site.
View Article and Find Full Text PDFSpecific cleavage of the nuclear pore complex protein Nup62 by a viral protease.
J Biol Chem
September 2010
Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona 85004, USA.
Previous work has shown that several nucleoporins, including Nup62 are degraded in cells infected with human rhinovirus (HRV) and poliovirus (PV) and that this contributes to the disruption of certain nuclear transport pathways. In this study, the mechanisms underlying proteolysis of Nup62 have been investigated. Analysis of Nup62 in lysates from HRV-infected cells revealed that Nup62 was cleaved at multiple sites during viral infection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!