Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1995;140(2):273–288. doi: 10.1007/BF01309862

Papain-like proteinase of turnip yellow mosaic virus: a prototype of a new viral proteinase group

M N Rozanov 1,2,3, G Drugeon 1, A -L Haenni 1
PMCID: PMC7086826  PMID: 7710355

Summary

Sequence comparisons predicted a potential papain-like proteinase domain in the N-terminal cleavage product (NRP) of the large nonstructural replicase polyprotein (RP) of turnip yellow mosaic virus (TYMV). Replacement of the predicted catalytic amino acids, Cys-783 by Ser, or of His-869 by Glu, abolished cleavage of the 206K RP into a ∼150K NRP and a ∼78K C-terminal product in reticulocyte lysates, while other substitutions exerted no apparent influence on proteolysis. The proteinase-deficient mutant RPs could not be cleaved in trans by as much as an eight-fold molar excess of wild-type proteinase. Deletion experiments have excluded the possible influence on autoproteolysis of amino acid sequences 1–708 and 982–1204 flanking the proteinase domain. Thus, the proteinase of TYMV with a papain-like dyad of essential amino acids has been mapped just upstream from the putative NTPase domain. Statistically significant sequence similarities with the TYMV proteinase were found for the similarly located domains of the replicase polyproteins of carlaviruses, capilloviruses, apple stem pitting virus and apple chlorotic leaf spot virus as well as for those of other tymoviruses and for the domain located downstream from the putative NTPase domain of the large polyprotein of beet necrotic yellow vein furovirus. All these domains are not significantly similar to other known proteinases, although they conserve papain-like Cys- and His-containing motifs. Thus these domains constitute a compact group of related enzymes, the tymo-like proteinases, within the proposedpapainlike proteinase supergroup. The resulting alignment of 10 tymo-like proteinase sequences has revealed a third highly conserved residue — Gly (Gly821 in TYMV RP) followed by a hydrophobic residue. We speculate that all the tymo-like proteinase domains of the viral replicative proteins may share common biochemical and biological features.

Keywords: Yellow Vein, Proteinase Domain, Spot Virus, Chlorotic Leaf, Apple Chlorotic Leaf Spot Virus

Footnotes

Reported in part at the NATO/EEC Course “Regulation of gene expression by animal viruses” Mallorca, May 30-June 8, 1992 and at the IX International Congress of Virology, Glasgow, August 8–13, 1993.

References

  • 1.Gorbalenya AE, Donchenko AP, Blinov VM, Koonin EV. Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases: a distinct protein superfamily with a common structural fold. FEBS Lett. 1989;243:103–114. doi: 10.1016/0014-5793(89)80109-7. [DOI] [PubMed] [Google Scholar]
  • 2.Bazan JF, Fletterick RJ. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proc Natl Acad Sci USA. 1988;85:7872–7876. doi: 10.1073/pnas.85.21.7872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Hardy WR, Strauss JH. Processing of nonstructural polyproteins of Sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both incis and intrans. J Virol. 1989;63:4653–4664. doi: 10.1128/jvi.63.11.4653-4664.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Gorbalenya AE, Koonin EV, Lai MM-C. Putative papain-related thiol proteases of positive-strand RNA viruses: identification of rubi- and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, α- and coronaviruses. FEBS Lett. 1991;288:201–205. doi: 10.1016/0014-5793(91)81034-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Goldbach R. Genome similarities between plant and animal RNA viruses. Microbiol Sci. 1987;4:197–202. [PubMed] [Google Scholar]
  • 6.Goldbach R. Plant viral proteinases. Semin Virol. 1990;1:335–346. [Google Scholar]
  • 7.Morch M-D, Boyer J-C, Haenni A-L. Overlapping open reading frames revealed by complete nucleotide sequencing of turnip yellow mosaic virus genomic RNA. Nucleic Acids Res. 1988;16:6157–6173. doi: 10.1093/nar/16.13.6157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Weiland JJ, Dreher TW. Cis-preferential replication of the turnip yellow mosaic virus RNA genome. Proc Natl Acad Sci USA. 1993;90:6095–6099. doi: 10.1073/pnas.90.13.6095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Bozarth CS, Weiland JJ, Dreher TW. Expression of ORF-69 of turnip yellow mosaic virus is necessary for viral spread in plants. Virology. 1992;187:124–130. doi: 10.1016/0042-6822(92)90301-5. [DOI] [PubMed] [Google Scholar]
  • 10.Weiland JJ, Dreher TW. Infectious TYMV RNA from cloned cDNA: effects in vitro and in vivo of point substitutions in the initiation codons of two extensively overlapping ORFs. Nucleic Acids Res. 1989;17:4675–4687. doi: 10.1093/nar/17.12.4675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Rozanov MN, Koonin EV, Gorbalenya AE. Conservation of the putative methyltransferase domain: a hallmark of the ‘Sindbis-like’ supergroup of positive-strand RNA viruses. J Gen Virol. 1992;73:2129–2134. doi: 10.1099/0022-1317-73-8-2129. [DOI] [PubMed] [Google Scholar]
  • 12.Rozanov MN, Morozov SYu, Skryabin KG. Unexpected close relationship between the large nonvirion proteins of filamentous potexviruses and spherical tymoviruses. Virus Genes. 1990;3:373–379. doi: 10.1007/BF00569044. [DOI] [PubMed] [Google Scholar]
  • 13.Morch M-D, Drugeon G, Szafranski P, Haenni A-L. Proteolytic origin of the 150-kilodalton protein encoded by turnip yellow mosaic virus genomic RNA. J Virol. 1989;63:5153–5158. doi: 10.1128/jvi.63.12.5153-5158.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Kadaré G, Drugeon G, Savithri HS, Haenni A-L. Comparison of the strategies of expression of five tymovirus RNAs by in vitro translation studies. J Gen Virol. 1992;73:493–498. doi: 10.1099/0022-1317-73-2-493. [DOI] [PubMed] [Google Scholar]
  • 15.Bransom KL, Weiland JJ, Dreher TW. Proteolytic maturation of the 206-kDa nonstructural protein encoded by turnip yellow mosaic virus RNA. Virology. 1991;184:351–358. doi: 10.1016/0042-6822(91)90851-2. [DOI] [PubMed] [Google Scholar]
  • 16.Koonin EV, Gorbalenya AE, Purdy MA, Rozanov MN, Reyes GR, Bradley DW. Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses. Proc Natl Acad Sci USA. 1992;89:8259–8263. doi: 10.1073/pnas.89.17.8259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Leontovich AM, Brodsky LI, Gorbalenya AE. Generation of a complete local similarity map for two biopolymer sequences (DOTHELIX program of the GENEBEE package) Biopolimery i Kletka. 1990;6:12–19. [Google Scholar]
  • 18.Corpet F. Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 1988;16:10881–10890. doi: 10.1093/nar/16.22.10881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Gorbalenya AE, Blinov VM, Donchenko AP, Koonin EV. An ATP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication. J Mol Evol. 1989;28:256–268. doi: 10.1007/BF02102483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Ding S, Keese P, Gibbs A. The nucleotide sequence of the genomic RNA of kennedya yellow mosaic tymovirus-Jervis Bay isolate: relationships with potex-and carlaviruses. J Gen Virol. 1990;71:925–931. doi: 10.1099/0022-1317-71-4-925. [DOI] [PubMed] [Google Scholar]
  • 21.Ding S-W, Keese P, Gibbs A. Nucleotide sequence of the ononis yellow mosaic tymovirus genome. Virology. 1989;172:555–563. doi: 10.1016/0042-6822(89)90198-0. [DOI] [PubMed] [Google Scholar]
  • 22.Osorio-Keese ME, Keese P, Gibbs A. Nucleotide sequence of the genome of eggplant mosaic tymovirus. Virology. 1989;172:547–554. doi: 10.1016/0042-6822(89)90197-9. [DOI] [PubMed] [Google Scholar]
  • 23.Srifah P, Keese P, Weiller G, Gibbs A. Comparisons of the genomic sequences of erysimum latent virus and other tymoviruses: a search for the molecular basis of their host specificities. J Gen Virol. 1992;73:1437–1447. doi: 10.1099/0022-1317-73-6-1437. [DOI] [PubMed] [Google Scholar]
  • 24.Zavriev SK, Kanyuka KV, Levay KE. The genome organization of potato virus M RNA. J Gen Virol. 1991;72:9–14. doi: 10.1099/0022-1317-72-1-9. [DOI] [PubMed] [Google Scholar]
  • 25.Jelkmann W. Nucleotide sequences of apple stem pitting virus and of the coat protein gene of a similar virus from pear associated with vein yellows disease and their relationship to potex- and carlaviruses. J Gen Virol. 1994;75:1535–1542. doi: 10.1099/0022-1317-75-7-1535. [DOI] [PubMed] [Google Scholar]
  • 26.German S, Candresse T, Lanneau M, Huet JC, Pernollet JC, Dunez J. Nucleotide sequence and genomic organization of apple chlorotic leaf spot closterovirus. Virology. 1990;179:104–112. doi: 10.1016/0042-6822(90)90279-z. [DOI] [PubMed] [Google Scholar]
  • 27.Yoshikawa N, Sasaki E, Kato M, Takahashi T. The nucleotide sequence of apple stem grooving capillovirus genome. Virology. 1992;191:98–105. doi: 10.1016/0042-6822(92)90170-t. [DOI] [PubMed] [Google Scholar]
  • 28.Bouzoubaa S, Quillet L, Guilley H, Jonard G, Richards K. Nucleotide sequence of beet necrotic yellow vein virus RNA-1. J Gen Virol. 1987;68:615–626. [Google Scholar]
  • 29.Ausubel FM, Brent R, Kingston ER, Moore DD, Seidman JG, Smith JA, Struhl K. Curr Prot Mol Biol. 1990;1:1.1–1.7. [Google Scholar]
  • 30.Boyer J-C, Drugeon G, Séron K, Morch-Devignes M-D, Agnès F, Haenni A-I. in vitro transcripts of turnip yellow mosaic virus encompassing a long 3′ extention or produced from a full-length cDNA clone harbouring a 2kb-long PCR-amplified segment are infectious. Res Virol. 1993;144:339–348. doi: 10.1016/s0923-2516(06)80049-x. [DOI] [PubMed] [Google Scholar]
  • 31.Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  • 32.Strauss JH, Strauss EG. Alphavirus proteinases. Semin Virol. 1990;1:347–356. [Google Scholar]
  • 33.Marr LD, Wang C-Y, Frey TK. Expression of the rubella virus nonstructural protein ORF and demonstration of proteolytic processing. Virology. 1994;198:586–592. doi: 10.1006/viro.1994.1070. [DOI] [PubMed] [Google Scholar]
  • 34.Baker SC, Yokomori K, Dong S, Carlisle R, Gorbalenya AE, Koonin EV, Lai MMC. Identification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus. J Virol. 1993;67:6056–6063. doi: 10.1128/jvi.67.10.6056-6063.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Snijder EJ, Wassenaar ALM, Spaan WJM. The 5′ end of the equine arteritis virus replicase gene encodes a papainlike cysteine protease. J Virol. 1992;66:7040–7048. doi: 10.1128/jvi.66.12.7040-7048.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Oh C-S, Carrington JC. Identification of essential residues in potyvirus proteinase HC-Pro by site-directed mutagenesis. Virology. 1989;173:692–699. doi: 10.1016/0042-6822(89)90582-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Choi GH, Pawlyk DM, Nuss DL. The autocatalytic protease p29 encoded by a hypovirulence-associated virus of the chestnut blight fungus resembles the potyvirus-encoded protease HC-Pro. Virology. 1991;183:747–752. doi: 10.1016/0042-6822(91)91004-z. [DOI] [PubMed] [Google Scholar]
  • 38.Shapira R, Nuss DL. Gene expression by a hypovirulence-associated virus of the chestnut blight fungus involves two papain-like proteinase activities. Essential residues and cleavage site requirements for p48 autoproteolysis. J Biol Chem. 1991;266:19419–19425. [PubMed] [Google Scholar]
  • 39.Kleina LG, Grubman MJ. Antiviral effects of a thiol protease inhibitor on foot-and-mouth disease virus. J Virol. 1992;66:7168–7175. doi: 10.1128/jvi.66.12.7168-7175.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Davidson AD, Prōls M, Schell J, Steinbiss H-H. The nucleotide sequence of RNA 2 of barley yellow mosaic virus. J Gen Virol. 1991;72:989–993. doi: 10.1099/0022-1317-72-4-989. [DOI] [PubMed] [Google Scholar]
  • 41.Kashiwazaki S, Minobe Y, Hibino H. Nucleotide sequence of barley yellow mosaic virus RNA 2. J Gen Virol. 1991;72:995–999. doi: 10.1099/0022-1317-72-4-995. [DOI] [PubMed] [Google Scholar]
  • 42.Stark R, Meyers G, Rumenapf T, Thiel H-J. Processing of pestivirus polyprotein: cleavage site between autoprotease and nucleocapsid protein of classical swine fever virus. J Virol. 1993;67:7088–7095. doi: 10.1128/jvi.67.12.7088-7095.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Koonin EV, Dolja VV. Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences. Crit Rev Biochem Mol Biol. 1993;28:375–430. doi: 10.3109/10409239309078440. [DOI] [PubMed] [Google Scholar]
  • 44.Ritonja A, Rowan AD, Buttle DJ, Rawlings ND, Turk V, Barrett AJ. Stem bromelain: amino acid sequence and implications for weak binding of cystatin. FEBS Lett. 1989;247:419–424. doi: 10.1016/0014-5793(89)81383-3. [DOI] [PubMed] [Google Scholar]
  • 45.Shirako Y, Strauss JH. Cleavage between nsP1 and nsP2 initiates the processing pathway of sindbis virus nonstructural polyprotein P123. Virology. 1990;177:54–64. doi: 10.1016/0042-6822(90)90459-5. [DOI] [PubMed] [Google Scholar]
  • 46.Carrington JC, Herndon KL. Characterization of the potyviral HC-Pro autoproteolytic cleavage site. Virology. 1992;187:308–315. doi: 10.1016/0042-6822(92)90319-K. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Hughes SA, Bonilla PJ, Weiss SR (1994) Analysis of MHV-A59 p28 cleavage site. 13th Annual Meeting of the American Society for Virology. Madison, Wisconsin, July 9–13. Abstract W45-2
  • 48.Dong S, Baker S (1994) Identification of the cleavage site of the first papain-like cysteine proteinase of murine coronavirus. 13th Annual Meeting of the American Society for Virology. Madison, Wisconsin, July 9–13 Abstract W45-3
  • 49.Schulz GE. Binding of nucleotides by proteins. Curr Opin Struct Biol. 1992;2:61–67. [Google Scholar]
  • 50.Bransom KL, Dreher TW. Identification of the essential cysteine and histidine residues of the turnip yellow mosaic virus protease. Virology. 1994;198:148–154. doi: 10.1006/viro.1994.1017. [DOI] [PubMed] [Google Scholar]
  • 51.Rozanov M, Drugeon G, Séron K, Haenni AL (1992) Papain-related proteinase of turnip yellow mosaic virus. NATO/EEC Course “Regulation of gene expression by animal viruses, Mallorca, May 30–June 8 Abstract S16
  • 52.Foster GD. The structure and expression of the genome of carlaviruses. Res Virol. 1992;143:103–113. doi: 10.1016/s0923-2516(06)80089-0. [DOI] [PubMed] [Google Scholar]
  • 53.Kao CC, Ahlquist P. Identification of the domains required for direct interaction of the helicase-like and polymeras-like RNA replication proteins of brome mosaic virus. J Virol. 1982;66:7293–7302. doi: 10.1128/jvi.66.12.7293-7302.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Lemm JA, Rice CM. Assembly of functional Sindbis virus RNA replication complexes: requirement for coexpression of P123 and P34. J Virol. 1993;67:1905–1915. doi: 10.1128/jvi.67.4.1905-1915.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Archives of Virology are provided here courtesy of Nature Publishing Group

RESOURCES