HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 35, 33220-33232, August 31, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/35/33220    most recent M104097200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ziebuhr, J. Articles by Gorbalenya, A. E. Search for Related Content PubMed PubMed Citation Articles by Ziebuhr, J. Articles by Gorbalenya, A. E. Social Bookmarking                      What's this?

The Autocatalytic Release of a Putative RNA Virus Transcription Factor from Its Polyprotein Precursor Involves Two Paralogous Papain-like Proteases That Cleave the Same Peptide Bond^*

John Ziebuhr^§, Volker Thiel, and Alexander E. Gorbalenya^¶

From the  Institute of Virology and Immunology, University of Würzburg, Versbacher Straße 7, 97078 Würzburg, Germany and ^¶ Advanced Biomedical Computing Center, Science Application International Corporation/NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201

The largest replicative protein of coronaviruses is known as p195 in the avian infectious bronchitis virus (IBV) and p210 (p240) in the mouse hepatitis virus. It is autocatalytically released from the precursors pp1a and pp1ab by one zinc finger-containing papain-like protease (PLpro) in IBV and by two paralogous PLpros, PL1pro and PL2pro, in mouse hepatitis virus. The PLpro-containing proteins have been recently implicated in the control of coronavirus subgenomic mRNA synthesis (transcription). By using comparative sequence analysis, we now show that the respective proteins of all sequenced coronaviruses are flanked by two conserved PLpro cleavage sites and share a complex (multi)domain organization with PL1pro being inactivated in IBV. Based upon these predictions, the processing of the human coronavirus 229E p195/p210 N terminus was studied in detail. First, an 87-kDa protein (p87), which is derived from a pp1a/pp1ab region immediately upstream of p195/p210, was identified in human coronavirus 229E-infected cells. Second, in vitro synthesized proteins representing different parts of pp1a were autocatalytically processed at the predicted site. Surprisingly, both PL1pro and PL2pro cleaved between p87 and p195/p210. The PL1pro-mediated cleavage was slow and significantly suppressed by a non-proteolytic activity of PL2pro. In contrast, PL2pro, whose proteolytic activity and specificity were established in this study, cleaved the same site efficiently in the presence of the upstream domains. Third, a correlation was observed between the overlapping substrate specificities and the parallel evolution of PL1pro and PL2pro. Collectively, our results imply that the p195/p210 autoprocessing mechanisms may be conserved among coronaviruses to an extent not appreciated previously, with PL2pro playing a major role. A large subset of coronaviruses may employ two proteases to cleave the same site(s) and thus regulate the expression of the viral genome in a unique way.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. J. Gadlage, R. L. Graham, and M. R. Denison Murine Coronaviruses Encoding nsp2 at Different Genomic Loci Have Altered Replication, Protein Expression, and Localization J. Virol., December 1, 2008; 82(23): 11964 - 11969. [Abstract] [Full Text] [PDF]

				B. W. Neuman, J. S. Joseph, K. S. Saikatendu, P. Serrano, A. Chatterjee, M. A. Johnson, L. Liao, J. P. Klaus, J. R. Yates III, K. Wuthrich, et al. Proteomics Analysis Unravels the Functional Repertoire of Coronavirus Nonstructural Protein 3 J. Virol., June 1, 2008; 82(11): 5279 - 5294. [Abstract] [Full Text] [PDF]

				M. A. Tijms, D. D. Nedialkova, J. C. Zevenhoven-Dobbe, A. E. Gorbalenya, and E. J. Snijder Arterivirus Subgenomic mRNA Synthesis and Virion Biogenesis Depend on the Multifunctional nsp1 Autoprotease J. Virol., October 1, 2007; 81(19): 10496 - 10505. [Abstract] [Full Text] [PDF]

				Z. Chen, Y. Wang, K. Ratia, A. D. Mesecar, K. D. Wilkinson, and S. C. Baker Proteolytic Processing and Deubiquitinating Activity of Papain-Like Proteases of Human Coronavirus NL63 J. Virol., June 1, 2007; 81(11): 6007 - 6018. [Abstract] [Full Text] [PDF]

				J. Ziebuhr, B. Schelle, N. Karl, E. Minskaia, S. Bayer, S. G. Siddell, A. E. Gorbalenya, and V. Thiel Human Coronavirus 229E Papain-Like Proteases Have Overlapping Specificities but Distinct Functions in Viral Replication J. Virol., April 15, 2007; 81(8): 3922 - 3932. [Abstract] [Full Text] [PDF]

				P. C. Y. Woo, M. Wang, S. K. P. Lau, H. Xu, R. W. S. Poon, R. Guo, B. H. L. Wong, K. Gao, H.-w. Tsoi, Y. Huang, et al. Comparative Analysis of Twelve Genomes of Three Novel Group 2c and Group 2d Coronaviruses Reveals Unique Group and Subgroup Features J. Virol., February 15, 2007; 81(4): 1574 - 1585. [Abstract] [Full Text] [PDF]

				R. L. Graham and M. R. Denison Replication of Murine Hepatitis Virus Is Regulated by Papain-Like Proteinase 1 Processing of Nonstructural Proteins 1, 2, and 3 J. Virol., December 1, 2006; 80(23): 11610 - 11620. [Abstract] [Full Text] [PDF]

				M.-P. Egloff, H. Malet, A. Putics, M. Heinonen, H. Dutartre, A. Frangeul, A. Gruez, V. Campanacci, C. Cambillau, J. Ziebuhr, et al. Structural and Functional Basis for ADP-Ribose and Poly(ADP-Ribose) Binding by Viral Macro Domains. J. Virol., September 1, 2006; 80(17): 8493 - 8502. [Abstract] [Full Text] [PDF]

				K. Ratia, K. S. Saikatendu, B. D. Santarsiero, N. Barretto, S. C. Baker, R. C. Stevens, and A. D. Mesecar Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme PNAS, April 11, 2006; 103(15): 5717 - 5722. [Abstract] [Full Text] [PDF]

				A. Putics, A. E. Gorbalenya, and J. Ziebuhr Identification of protease and ADP-ribose 1''-monophosphatase activities associated with transmissible gastroenteritis virus non-structural protein 3. J. Gen. Virol., March 1, 2006; 87(Pt 3): 651 - 656. [Abstract] [Full Text] [PDF]

				C. Galan, L. Enjuanes, and F. Almazan A Point Mutation within the Replicase Gene Differentially Affects Coronavirus Genome versus Minigenome Replication J. Virol., December 15, 2005; 79(24): 15016 - 15026. [Abstract] [Full Text] [PDF]

				H. A. Lindner, N. Fotouhi-Ardakani, V. Lytvyn, P. Lachance, T. Sulea, and R. Menard The Papain-Like Protease from the Severe Acute Respiratory Syndrome Coronavirus Is a Deubiquitinating Enzyme J. Virol., December 15, 2005; 79(24): 15199 - 15208. [Abstract] [Full Text] [PDF]

				S. R. Weiss and S. Navas-Martin Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus Microbiol. Mol. Biol. Rev., December 1, 2005; 69(4): 635 - 664. [Abstract] [Full Text] [PDF]

				R. L. Graham, A. C. Sims, S. M. Brockway, R. S. Baric, and M. R. Denison The nsp2 Replicase Proteins of Murine Hepatitis Virus and Severe Acute Respiratory Syndrome Coronavirus Are Dispensable for Viral Replication J. Virol., November 1, 2005; 79(21): 13399 - 13411. [Abstract] [Full Text] [PDF]

				A. Putics, W. Filipowicz, J. Hall, A. E. Gorbalenya, and J. Ziebuhr ADP-Ribose-1"-Monophosphatase: a Conserved Coronavirus Enzyme That Is Dispensable for Viral Replication in Tissue Culture J. Virol., October 15, 2005; 79(20): 12721 - 12731. [Abstract] [Full Text] [PDF]

				C.-N. Chen, C. P. C. Lin, K.-K. Huang, W.-C. Chen, H.-P. Hsieh, P.-H. Liang, and J. T.-A. Hsu Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3'-digallate (TF3) Evid. Based Complement. Altern. Med., June 1, 2005; 2(2): 209 - 215. [Abstract] [Full Text] [PDF]

				Z. R. Yang Mining SARS-CoV protease cleavage data using non-orthogonal decision trees: a novel method for decisive template selection Bioinformatics, June 1, 2005; 21(11): 2644 - 2650. [Abstract] [Full Text] [PDF]

				T. Sulea, H. A. Lindner, E. O. Purisima, and R. Menard Deubiquitination, a New Function of the Severe Acute Respiratory Syndrome Coronavirus Papain-Like Protease? J. Virol., April 1, 2005; 79(7): 4550 - 4551. [Full Text] [PDF]

				L. Vijgen, E. Keyaerts, E. Moes, I. Thoelen, E. Wollants, P. Lemey, A.-M. Vandamme, and M. Van Ranst Complete Genomic Sequence of Human Coronavirus OC43: Molecular Clock Analysis Suggests a Relatively Recent Zoonotic Coronavirus Transmission Event J. Virol., February 1, 2005; 79(3): 1595 - 1604. [Abstract] [Full Text] [PDF]

				B. H. Harcourt, D. Jukneliene, A. Kanjanahaluethai, J. Bechill, K. M. Severson, C. M. Smith, P. A. Rota, and S. C. Baker Identification of Severe Acute Respiratory Syndrome Coronavirus Replicase Products and Characterization of Papain-Like Protease Activity J. Virol., December 15, 2004; 78(24): 13600 - 13612. [Abstract] [Full Text] [PDF]

				K. A. Ivanov, T. Hertzig, M. Rozanov, S. Bayer, V. Thiel, A. E. Gorbalenya, and J. Ziebuhr Major genetic marker of nidoviruses encodes a replicative endoribonuclease PNAS, August 24, 2004; 101(34): 12694 - 12699. [Abstract] [Full Text] [PDF]

				K. A. Ivanov and J. Ziebuhr Human Coronavirus 229E Nonstructural Protein 13: Characterization of Duplex-Unwinding, Nucleoside Triphosphatase, and RNA 5'-Triphosphatase Activities J. Virol., July 15, 2004; 78(14): 7833 - 7838. [Abstract] [Full Text] [PDF]

				K. A. Ivanov, V. Thiel, J. C. Dobbe, Y. van der Meer, E. J. Snijder, and J. Ziebuhr Multiple Enzymatic Activities Associated with Severe Acute Respiratory Syndrome Coronavirus Helicase J. Virol., June 1, 2004; 78(11): 5619 - 5632. [Abstract] [Full Text] [PDF]

				M. R. Denison, B. Yount, S. M. Brockway, R. L. Graham, A. C. Sims, X. Lu, and R. S. Baric Cleavage between Replicase Proteins p28 and p65 of Mouse Hepatitis Virus Is Not Required for Virus Replication J. Virol., June 1, 2004; 78(11): 5957 - 5965. [Abstract] [Full Text] [PDF]

				V. Thiel, K. A. Ivanov, A. Putics, T. Hertzig, B. Schelle, S. Bayer, B. Weissbrich, E. J. Snijder, H. Rabenau, H. W. Doerr, et al. Mechanisms and enzymes involved in SARS coronavirus genome expression J. Gen. Virol., September 1, 2003; 84(9): 2305 - 2315. [Abstract] [Full Text] [PDF]

				A. Kanjanahaluethai, D. Jukneliene, and S. C. Baker Identification of the Murine Coronavirus MP1 Cleavage Site Recognized by Papain-Like Proteinase 2 J. Virol., July 1, 2003; 77(13): 7376 - 7382. [Abstract] [Full Text] [PDF]

				L. F. P. Ng and D. X. Liu Membrane Association and Dimerization of a Cysteine-Rich, 16-Kilodalton Polypeptide Released from the C-Terminal Region of the Coronavirus Infectious Bronchitis Virus 1a Polyprotein J. Virol., May 13, 2002; 76(12): 6257 - 6267. [Abstract] [Full Text] [PDF]

				A. Hegyi, A. Friebe, A. E. Gorbalenya, and J. Ziebuhr Mutational analysis of the active centre of coronavirus 3C-like proteases J. Gen. Virol., March 1, 2002; 83(3): 581 - 593. [Abstract] [Full Text] [PDF]

				A. Hegyi and J. Ziebuhr Conservation of substrate specificities among coronavirus main proteases J. Gen. Virol., March 1, 2002; 83(3): 595 - 599. [Abstract] [Full Text] [PDF]

				V. N. Chouljenko, X. Q. Lin, J. Storz, K. G. Kousoulas, and A. E. Gorbalenya Comparison of genomic and predicted amino acid sequences of respiratory and enteric bovine coronaviruses isolated from the same animal with fatal shipping pneumonia J. Gen. Virol., December 1, 2001; 82(12): 2927 - 2933. [Abstract] [Full Text] [PDF]