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An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication

Journal of Molecular Evolution volume 28, pages 256–268 (1989)Cite this article

Summary

NTP-motif, a consensus sequence previously shown to be characteristic of numerous NTP-utilizing enzymes, was identified in nonstructural proteins of several groups of positive-strand RNA viruses. These groups include picorna-, alpha-, and coronaviruses infecting animals and como-, poty-, tobamo-, tricorna-, hordei-, and furoviruses of plants, totalling 21 viruses. It has been demonstrated that the viral NTP-motif-containing proteins constitute three distinct families, the sequences within each family being similar to each other at a statistically highly significant level. A lower, but still valid similarity has also been revealed between the families. An overall alignment has been generated, which includes several highly conserved sequence stretches. The two most prominent of the latter contain the socalled “A” and “B” sites of the NTP-motif, with four of the five invariant amino acid residues observed within these sequences. These observations, taken together with the results of comparative analysis of the positions occupied by respective proteins (domains) in viral multidomain proteins, suggest that all the NTP-motif-containing proteins of positive-strand RNA viruses are homologous, constituting a highly diverged monophyletic group. In this group the “A” and “B” sites of the NTP-motif are the most conserved sequences and, by inference, should play the principal role in the functioning of the proteins. A hypothesis is proposed that all these proteins posses NTP-binding capacity and possibly NTPase activity, performing some NTP-dependent function in viral RNA replication. The importance of phylogenetic analysis for the assessment of the significance of the occurrence of the NTP-motif (and of sequence motifs of this sort in general) in proteins is emphasized.

References

  • Ahlquist P, Dasgupta R, Kaesberg P (1984) Nucleotide sequence of the brome mosaic virus genome and its implications for viral replication. J Mol Biol 172:369–383

    PubMed  Google Scholar 

  • Ahlquist P, Strauss EG, Rice CM, Strauss JH, Haseloff J, Zimmern D (1985) Sindbis virus proteins nsP1 and nsP2 contain homology to nonstructural proteins from several RNA plant viruses. J Virol 53:536–542

    PubMed  Google Scholar 

  • Allison R, Johnston RE, Dougherty WG (1986) The nucleotide sequence of the coding region of tobacco etch virus genomic RNA: evidence for the synthesis of a single polyprotein. Virology 154:9–20

    Article  Google Scholar 

  • Anton IA, Lane DP (1986) Non-structural protein 1 of parvoviruses: homology to purine nucleotide using proteins and early proteins of papovaviruses. Nucleic Acids Res 14:7613

    Google Scholar 

  • Argos P, Leberman R (1985) Homologies and anomalies in primary structural patterns of nucleotide binding proteins. Eur J Biochem 152:651–656

    Article  PubMed  Google Scholar 

  • Argos P, Kamer G, Nicklin MJH, Wimmer E (1984) Similarity in gene organization and homology between proteins of animal picornaviruses and a plant comovirus suggest common ancestry of these virus families. Nucleic Acids Res 12:7251–7267

    PubMed  Google Scholar 

  • Astell CR, Mol CL, Anderson WF (1987) Structural and functional homology of parvovirus and papovavirus polypeptides. J Gen Virol 68:885–893

    PubMed  Google Scholar 

  • Blumenthal T (1979) Qβ RNA replicase and protein synthesis elongation factors EF-Tu and EF-Ts. Methods Enzymol 60: 628–638

    PubMed  Google Scholar 

  • Boursnell MEG, Brown TDK, Foulds IJ, Green PF, Tomley FM, Binns MM (1987) Completion of the sequence of the genome of the coronavirus avian infectious bronchitis virus. J Gen Virol 68:57–77

    PubMed  Google Scholar 

  • Bouzoubaa S, Ziegler V, Beck D, Guilley H, Richards K, Jonard G (1986) Nucleotide sequence of beet necrotic yellow vein virus RNA-2. J Gen Virol 67:1689–1700

    Google Scholar 

  • Bouzoubaa S, Quillet L, Guilley H, Jonard G, Richards K (1987) Nucleotide sequence of beet necrotic yellow vein virus RNA-1. J Gen Virol 68:615–626

    Google Scholar 

  • Bradley MK, Smith TF, Lathrop FH, Livingston DM (1987) Consensus topography in the ATP binding site of the SV40 and polyomavirus large tumour antigens. Proc Natl Acad Sci USA 84:4026–4030

    PubMed  Google Scholar 

  • Carrington JC, Dougherty WG (1987) Small nuclear inclusion protein encoded by a plant potyvirus genome is a protease. J Virol 61:2540–2548

    Google Scholar 

  • Carroll AR, Rowlands DJ, Clarke BE (1984) The complete nucleotide sequence of the RNA coding for the primary translation product of foot and mouth disease virus. Nucleic Acids Res 12:2461–2472

    PubMed  Google Scholar 

  • Castle E, Leidner U, Nowak T, Wengler G, Wengler G (1986) Primary structure of the West Nile flavivirus genome region coding for all nonstructural proteins. Virology 149:10–26

    Article  PubMed  Google Scholar 

  • Chen C, Chin JE, Ueda K, Clark DP, Pastan I, Gettesman MM, Roninson IB (1986) Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47:381–389

    Article  PubMed  Google Scholar 

  • Clertant P, Seif I 1984) A common function for polyomavirus large-T and papillomavirus E1 proteins. Nature 311:276–279

    Article  PubMed  Google Scholar 

  • Cornelissen BJC, Bol JF (1984) Homology between the proteins encoded by tobacco mosaic virus and two tricornaviruses. Plant Mol Biol 3:379–384

    Article  Google Scholar 

  • Cornelissen BJC, Brederode FT, Moormann RJM, Bol JF (1983) Complete nucleotide sequence of alfalfa mosaic virus RNA 1. Nucleic Acids Res 11:1253–1265

    PubMed  Google Scholar 

  • Dayhoff MO, Barker WC, Hunt LT (1983) Establishing homologies in protein sequences. Methods Enzymol 91:524–549

    PubMed  Google Scholar 

  • Dever TE, Glynias MJ, Merrick WC (1987) GTP-binding domains: three consensus sequence elements with distinct spacing. Proc Natl Acad Sci USA 84:1814–1818

    PubMed  Google Scholar 

  • Domier LL, Franklin KM, Shahabuddin M, Hellmann GM, Overmeyer JH, Hiremath ST, Siaw MFE, Lomonosoff GP, Shaw JG, Rhoads RE (1986) The nucleotide sequence of tobacco vein mottling virus RNA. Nucleic Acids Res 14: 5417–5430

    PubMed  Google Scholar 

  • Domier LL, Shaw JG, Rhoads RE (1987) Potyviral proteins share amino acid sequence homology with picorna-, como- and caulimoviral proteins. Virology 158:20–27

    Article  Google Scholar 

  • Doolittle RF (1981) Similar amino acid sequences: chance or common ancestry? Science 214:149–159

    PubMed  Google Scholar 

  • Doolittle RF (1986a) Protein sequence data banks: the continuing search for related sequences. In: Inouye M (ed) Protein engineering. Academic Press, New York, pp 15–27

    Google Scholar 

  • Doolittle RF (1986b) Of URFs and ORFs. A primer on how to analyze derived amino acid sequences. Univ. Science Books, Mill Valley CA

    Google Scholar 

  • Doolittle RF, Johnson MS, Husain I, Van Houten B, Thomas DC, Sancar A (1986) Domainal evolution of a prokaryotic DNA repair protein and its relationship to active transport proteins. Nature 323:451–453

    Article  PubMed  Google Scholar 

  • Evans RK, Haley BE, Roty DA (1985) Photoaffinity labeling of a viral induced protein from tobacco. J Biol Chem 260: 7800–7804

    PubMed  Google Scholar 

  • Finch PW, Storey A, Chapman KE, Brown K, Hickson ID, Emmerson PT (1986a) Complete nucleotide sequence of theEscherichia coli recB gene. Nucleic Acid. Res 14:8573–8582

    PubMed  Google Scholar 

  • Finch PW, Storey A, Brown K, Hickson ID, Emmerson PT (1986b) Complete nucleotide sequence of recD, the structural gene for the α subunit of exonuclease V ofEscherichia coli. Nucleic Acids Res 14:8583–8594

    PubMed  Google Scholar 

  • Forster RLS, Bevan MW, Harbison S-A, Gardner RC (1988) The complete nucleotide sequence of the potexvirus white clover mosaic virus. Nucleic Acids Res 16:290–303

    Google Scholar 

  • Franssen H, Leunissen J, Goldbach R, Lomonosoff GP, Zimmern D (1984) Homologous sequences in non-structural proteins from cowpea mosaic virus and picornaviruses. EMBO J 3:855–861

    Google Scholar 

  • Fry DC, Kuby SA, Mildvan AS (1986) ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins. Proc Natl Acad Sci USA 83:907–911

    PubMed  Google Scholar 

  • Gay NJ, Walker JE (1983) Homology between human bladder cacrinoma oncogene product and mitochondrial ATP-synthase. Nature 301:262–264

    Article  PubMed  Google Scholar 

  • Gilchrist CA, Denhardt DT (1987)Escherichia coli rep gene: sequence of the gene, the encoded helicase, and its homology with uvrD. Nucleic Acids Res 15:465–475

    PubMed  Google Scholar 

  • Goelet P, Lomonosoff GP, Butler PJG, Akam ME, Gait MJ, Karn J (1982) Nucleotide sequence of tobacco mosaic virus RNA. Proc Natl Acad Sci USA 79:5818–5822

    PubMed  Google Scholar 

  • Goldbach R (1986) Molecular evolution of plant RNA viruses. Annu Rev Phytopathol 24:289–310

    Article  Google Scholar 

  • Gorbalenya AE, Blinov VM, Koonin EV (1985) Prediction of nucleotide-binding properties of virus-specific proteins from their primary structure. Molek Genetika No. 11:30–36 [in Russian]

    Google Scholar 

  • Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM (1987) Two segments of barley stripe mosaic virus genomic RNA encode two homologous proteins which probably possess NTPase activity. Molek Biol 21:1566–1572 [in Russian]

    Google Scholar 

  • Gorbalenya AE, Koonin EV (1988) One more conserved sequence motif in helicases. Nucleic Acids Res 16 (in press)

  • Gorbalenya AE, Koonin EV, Blinov VM, Donchenko AP (1988a) Sobemovirus genome appears to encode a serine protease related to cysteine proteases of picornaviruses. FEBS Letters (in press)

  • Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM (1988b) A conserved NTP-motif in putative helicases. Nature 333:22

    Article  Google Scholar 

  • Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM (1988c) A novel superfamily of nucleoside triphosphatebinding motif containing proteins which are probably involved in duplex unwinding in DNA and RNA replication and recombination. FEBS Letters (in press)

  • Gros P, Croop J, Housman D (1986) Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell 47:371–380

    Article  PubMed  Google Scholar 

  • Gustafson G, Armour SL (1986) The complete nucleotide sequence of RNAβ from the type strain of barley stripe mosaic virus. Nucleic Acids Res 14:3895–3909

    PubMed  Google Scholar 

  • Halliday K (1984) Regional homology in GTP-binding protooncogene and elongation factors. J Cyclic Nucleotide Protein Phosphorylation Res 9:435–448

    Google Scholar 

  • Hamilton WDO, Boccara M, Robinson DJ, Baulcombe DC (1987) The complete nucleotide sequence of tobacco rattle virus RNA-I. J Gen Virol 68:2563–2575

    PubMed  Google Scholar 

  • Higgins CF, Hiles ID, Salmond GPC, Gill DR, Downie JA, Evans IJ, Holland IB, Gray L, Buckel SD, Bell AW, Hermodson MA (1986) A family of related ATP-binding subunits coupled to many distinct biological processes in bacteria. Nature 323:448–450

    Article  PubMed  Google Scholar 

  • Hodgman TC (1986) The elucidation of protein function from its amino acid sequence. CABIOS 2:181–187

    PubMed  Google Scholar 

  • Hodgman TC (1988) A new superfamily of replicative proteins. Nature 333:22–23, 578

    Article  Google Scholar 

  • Husain I, van Houten B, Thomas DC, Sancar A (1986) Sequences ofEscherichia coli uvrA gene and protein reveal two potential ATP binding sites. J Biol Chem 261:4895–4901

    PubMed  Google Scholar 

  • Jurnak F (1985) Structure of the GDP domain of EF-Tu and location of the amino acids homologous to ras oncogene proteins. Science 230:32–36

    PubMed  Google Scholar 

  • Kamer G, Argos P (1984) Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses. Nucleic Acids Res 12:7269–7282

    PubMed  Google Scholar 

  • Koonin EV, Gorbalenya AE, Chumakov KM, Donchenko AP, Blinov VM (1987) Evolution of RNA-dependent RNA polymerases of positive strand RNA viruses. Molek Genetika No. 7:27–39 [in Russian]

    Google Scholar 

  • Koonin EV, Chumakov KM, Yushmanov SV, Gorbalenya AE (1988) Evolution of RNA-dependent RNA polymerases of positive strand RNA viruses: a comparison of phylogenetic trees generated by different methods. Molek Genetika No. 3: 16–19 [in Russian]

    Google Scholar 

  • Krayev AS, Morozov SY, Lukasheva LI, Rozanov MN, Chernov BK Simonova ML, Golova YB, Belzhelarskaya SN, Pozmogova GE, Skryabin KG, Atabekov JG (1988) The complete nucleotide sequence and genomic organization of potato X virus. Dokl Akad Nauk SSSR 300:711–716 [in Russian]

    PubMed  Google Scholar 

  • La Cour TFM, Nyborg J, Thirup S, Clark BFC (1985) Structural details of the binding of guanosine diphosphate to elongation factor Tu fromEscherichia coli as studied by X-ray crystallography. EMBO J 4:2385–2388

    PubMed  Google Scholar 

  • Lindeberg AM, Stalhandske POK, Pettersson U (1987) Genome of coxsackievirus B3. Virology 156:50–63

    Article  PubMed  Google Scholar 

  • Lomonosoff GP, Shanks M (1983) The nucleotide sequence of cowpea mosaic B RNA. EMBO J 2:2253–2258

    Google Scholar 

  • Matthews REF (1982) Classification and nomenclature of viruses. Intervirology 17:1–199

    PubMed  Google Scholar 

  • Möller W, Amons R (1985) Phosphate-binding sequences in nucleotide-binding proteins. FEBS Lett 186:1–7

    Article  PubMed  Google Scholar 

  • Morozov SY, Rupasov VV (1985) On the possibility of a common origin of the genes encoding the RNA polymerases of bacterial, plant and animal positive strand RNA viruses. Biol Nauki No. 10:19–23 [in Russian]

    Google Scholar 

  • Najarian R, Caput D, Gee W, Potter SJ, Renard A, Merryweather J, Van Nest G, Dina D (1985) Primary structure and gene organization of human hepatitis A virus. Proc Natl Acad Sci USA 82:2627–2631

    PubMed  Google Scholar 

  • Palmenberg AG, Kirby EM, Janda MR, Drake NL, Duke GM, Potratz KF, Collett MS (1984) The nucleotide abd deduced amino acid sequences of the encephalomyocarditis viral polyprotein coding region. Nucleic Acids Res 12:2969–2985

    PubMed  Google Scholar 

  • Pevear DC, Calenoff M, Rozhon E, Lipton HL (1987) Analysis of the complete nucleotide sequence of the picornavirus Theiler's murine encephalomyelitis virus (TMEV) indicates that it is closely related to cardioviruses. J Virol 61:1507–1516

    PubMed  Google Scholar 

  • Pincus SV, Diamond DC, Emini EA, Wimmer E (1986) Guanidine-selected mutants of poliovirus: mapping of point mutations to polypeptide 2C. J Virol 57:638–646

    PubMed  Google Scholar 

  • Pincus SE, Rohl H, Wimmer E (1987) Guanidine-dependent mutants of poliovirus: identification of three classes with different growth requirements. Virology 157:83–88

    Article  PubMed  Google Scholar 

  • Pozdnyakov VI, Pankov YA (1981) Accelerated method for comparing amino acid sequences with allowance for possible gaps. Plotting optimum correspondence paths. Int J Pept Protein Res 17:284–291

    PubMed  Google Scholar 

  • Racaniello V, Baltimore D (1981) Molecular cloning of poliovirus cDNA and determination of the complete nucleotide sequence of the viral genome. Proc Natl Acad Sci USA 78: 4887–4891

    PubMed  Google Scholar 

  • Rezaian MA, Williams RHV, Symons R (1985) Nucleotide sequence of cucumber mosaic virus RNA 1. Eur J Biochem 150:331–339

    Article  PubMed  Google Scholar 

  • Rice CM, Lenches EM, Eddy SR, Shin SJ, Sheets R, Strauss JH (1985) Nucleotide sequence of yellow fever virus implications for flavivirus gene expression and evolution. Science 229:726–733

    PubMed  Google Scholar 

  • Rupasov VV, Afanasiev BN, Adyshev DA, Kozlov YV (1986) Nucleotide sequence of 3′-terminal regions of barley stripe mosaic virus RNAs 1 and 3. Dokl Akad Nauk SSSR 288: 1237–1241 [in Russian]

    Google Scholar 

  • Sankoff D (1972) Matching sequences under deletion/insertion constraints. Proc Natl Acad Sci USA 69:4–6

    PubMed  Google Scholar 

  • Skern T, Sommergruber W, Blaas D, Gruendler P, Fraundorfer F, Pieler C, Fogy I, Kuechler E (1985) Human rhinovirus 2: complete nucleotide sequence and proteolytic processing signals in the capsid protein region. Nucleic Acids Res 13: 2111–2126

    PubMed  Google Scholar 

  • Staden R (1982) An interactive graphics programme for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res 10:2951–2961

    PubMed  Google Scholar 

  • Stanway G, Hughes PJ, Mountford RC, Minor PD, Almond JW (1984) The complete sequence of a common cold virus: human rhinovirus 14. Nucleic Acids Res 12:7859–7875

    PubMed  Google Scholar 

  • Strauss EG, Rice CM, Strauss JH (1984) Complete nucleotide sequence of the genomic RNA of Sindbis virus. Virology 133: 92–110

    Article  PubMed  Google Scholar 

  • Takkinen A (1986) Complete nucleotide sequence of the nonstructural protein genes of Semliki Forest virus. Nucleic Acids Res 14:5667–5682

    PubMed  Google Scholar 

  • Walker JE, Saraste M, Runswick MJ, Gay NJ (1982) Distantly related sequences in the α-and β-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 2:945–951

    Google Scholar 

  • Wu S, Rinehart CA, Kaesberg P (1987) Sequence and organization of southern bean mosaic virus genomic RNA. Virology 161:73–80

    Article  PubMed  Google Scholar 

  • Yaegashi T, Vakharia VN, Page K, Sasaguri Y, Feighny R, Padmanabhan R (1986) Partial sequence analysis of cloned dengue virus type 2 genome. Gene 46:257–267

    Article  PubMed  Google Scholar 

  • Yin K-C, Blinkova A, Walker JR (1986) Nucleotide sequence of theEscherichia coli replication gene dnaZX. Nucleic Acids Res 14:6541–6549

    PubMed  Google Scholar 

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  1. Institute of Poliomyelitis and Viral Encephalitides of the USSR Academy of Medical Sciences, 142782, Moscow Region, USSR

    Alexander E. Gorbalenya, Vladimir M. Blinov, Alexei P. Donchenko & Eugene V. Koonin

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  1. Alexander E. Gorbalenya
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  2. Vladimir M. Blinov
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  3. Alexei P. Donchenko
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  4. Eugene V. Koonin
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Gorbalenya, A.E., Blinov, V.M., Donchenko, A.P. et al. An NTP-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 28, 256–268 (1989). https://doi.org/10.1007/BF02102483

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  • DOI: https://doi.org/10.1007/BF02102483

Key words

  • Evolution
  • Multiple sequence alignment
  • NTP binding
  • Phylogenetic analysis
  • Positive-strand RNA viruses