Structure of a Human Rhinovirus Complexed with its Receptor Molecule

  • Norman H. Olson
  • Prasanna R. Kolatkar
  • Marcos A. Oliveira
  • R. Holland Cheng
  • Jeffrey M. Greve
  • Alan McClelland
  • Timothy S. Baker
  • Michael G. Rossmann
Part of the NATO ASI Series book series (NSSA, volume 240)


Human rhinoviruses are one of the major causes of the common cold. They, like other picornaviruses, are icosahedral assemblies of 60 protomers that envelope a single, positive-sense strand of RNA. Each protomer consists of four polypeptides, VP1 — VP4. The three external viral proteins (VP1 — VP3) each have an approximate molecular weight of 30,000 and a similar folding topology (Rossmann et al., 1985; Hogle et al., 1985). The external viral radius is ~150 Å and the total molecular weight is roughly 8.5 × 106. A surface depression, or canyon, that is about 12 A deep and 12 – 15 Å wide, encircles each pentagonal vertex (Fig. 1C). Residues lining the canyon are more conserved than other surface residues among rhinovirus serotypes3. The most variable surface residues are at the sites of attachment of neutralizing antibodies (Rossmann et al., 1985; Sherry and Ruecker, 1985; Sherry et al., 1986). It has been proposed that the cellular receptor molecule recognized by the virus binds to conserved residues in the canyon, thus escaping neutralization by host antibodies that are too big to penetrate into that region. This hypothesis (Rossmann et al., 1985; Rossmann, 1989) is supported by site-directed mutagenesis of residues lining the canyon which alters the ability of the virus to attach to HeLa cell membranes (Colonno et al., 1988). Also, conformational changes in the floor of the canyon, produced by certain antiviral agents that bind into a pocket beneath the canyon floor, inhibit viral attachment to cellular membranes (Pevear et al., 1985). Conservation of the viral attachment site inside a surface depression has been observed for Mengo (Kim et al., 1990) and influenza virus (Weis et al., 1988; Colman et al., 1983).


Influenza Virus Cryoelectron Microscopy Virus Binding Human Rhinovirus Canyon Floor 
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  1. Abraham, G. and Colonno, R.J., 1984, Many rhinovirus serotypes share the same cellular receptor, J Virol. 51: 340–345.PubMedGoogle Scholar
  2. Altermeyer, R., Murdin, A.D., Harber, J.J. and Wimmer, E., 1991, Construction and characterization of a poliovirus/rhinovirus antigenic hybrid, Virology. 184: 636–644.CrossRefGoogle Scholar
  3. Arthos, J., Deen, K.C., Chaikin, M.A., Fornwald, J.A., Sathe, G., Sattentau, Q.J., Clapham, P.R., Weiss, R.A., McDougal, J.S., Pietropaolo, C., Axel, R., Truneh, A., Maddon, P.J. and Sweet, R.W., 1989, Identification of the residues in human CD4 critical for the binding of HIV, Cell. 57:469–481.PubMedCrossRefGoogle Scholar
  4. Badger, J., Krishnaswamy, S., Kremer, M.J., Oliveira, M.A., Rossmann, M.G., Heinz, B.A., Rueckert, R.R., Dutko, F.J. and McRinlay, M.A., 1989, The three-dimensional structures of drug-resistant mutants of human rhinovirus 14, J Mol Biol. 207: 163–174.PubMedCrossRefGoogle Scholar
  5. Badger, J., Minor, I., Kremer, M.J., Oliveira, M.A., Smith, T.J., Griffith, J.P., Guerin, D.M.A., Krishnaswamy, S., Luo, M., Rossmann, M.G., McKinlay, M.A., Diana, G.D., Dutko, F.J., Fancher, M., Rueckert, R.R. and Heinz, B.A., 1988, Structural analysis of a series of antiviral agents complexed with human rhinovirus 14, Proc Natl Acad Sci USA. 85: 3304–3308.PubMedCrossRefGoogle Scholar
  6. Baker, T.S., Newcomb, W.W., Olson, N.H., Cowsert, L.M., Olson, C. and Brown, J.C., 1991, Structures of bovine and human papillomaviruses: analysis cryoelectron microscopy and three-dimensional image reconstruction, Biophys J. 60: 1445–1456.PubMedCrossRefGoogle Scholar
  7. Colman, P.M., Varghese, J.N., and Laver, W.G., 1983, Structure of the catalytic and antigenic sites in influenza virus neuraminidase, Nature. 303: 41–44.PubMedCrossRefGoogle Scholar
  8. Colonno, R.J., Condra, J.H., Mizutani, S., Callahan, P.L., Davies, M.E. and Murcko, M.A., 1988, Evidence for the direct involvement of the rhinovirus canyon in receptor binding, Proc Natl Acad Sci USA. 85:5449–5453.PubMedCrossRefGoogle Scholar
  9. Cheng, R.H., Olson, N.H. and Baker, T.S., 1992, Cauliflower mosaic virus: a 420 subunit (T = 7), multilayer structure, Virology. 186: 655–668.PubMedCrossRefGoogle Scholar
  10. Dalgleish, A.G., Beverly, P.C.L., Clapham, P.R., Crawford, D.H., Greaves, M.F. and Weiss, R.A., 1984, The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus, Nature (London). 312: 763–767.CrossRefGoogle Scholar
  11. de Vos, A.M., Ultsch, M. and Kossiakoff, A.A., 1992, Human growth hormone and extracellular domain of its receptor: crystal structure of the complex, Science. 255: 306–312.PubMedCrossRefGoogle Scholar
  12. Diana, G.D., McKinlay, M.A., Otto, M.J., Alullian, V. and Oglesby, C., 1985, [[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of viral uncoating, J Med Chem. 28: 1906–1910.PubMedCrossRefGoogle Scholar
  13. Filman, D.J., Syed, R., Chow, M., Macadam, A.J., Minor, P.D. and Hogle, J.M., 1989, Structural factors that control conformational transitions and serotype specificity in type 3 poliovirus, EMBO J. 8: 1567–1579.PubMedGoogle Scholar
  14. Freistadt, M.S. and Racaniello, V.R., 1991, Mutational analysis of the cellular receptors for poliovirus, J Virol. 65: 3873–3876.PubMedGoogle Scholar
  15. Giranda, V.L., Chapman, M.S. and Rossmann, M.G., 1990, Modeling of the human intercellular adhesion molecule-1, the human rhinovirus major group receptor, Proteins. 7: 227–233.PubMedCrossRefGoogle Scholar
  16. Greve, J.M., Davis, G., Meyer, A.M., Forte, C.P., Yost, S.C., Marlor, C.W., Kamarck, M.E. and McClelland, A., 1989, The major human rhinovirus receptor is ICAM-1, Cell. 56: 839–847.PubMedCrossRefGoogle Scholar
  17. Greve, J.M., Forte, C.P., Marlor, C.W., Meyer, A.M., Hoover-Litty, H., Wunderlich, D. and McClelland, A., 1991, Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1, J Virol. 65: 6015–6023.PubMedGoogle Scholar
  18. Gromeier, M. and Wetz, K.J., 1990, Kinetics of poliovirus uncoating in HeLa cells in a nonacidic environment, J Virol. 64: 3590–3597.PubMedGoogle Scholar
  19. Heinz, B.A., Rueckert, R.R., Shepard, D.A., Dutko, F.J., McKinlay, M.A., Fancher, M., Rossmann, M.G., Badger, J. and Smith, T.J., 1989, NGenetic and molecular analyses of spontaneous mutants of human rhinovirus 14 are resistant to an antiviral compound, J Virol. 63: 2476–2485.PubMedGoogle Scholar
  20. Hogle, J.M., Chow, M. and Filman, D.J., 1985, Three-dimensional structure of poliovirus at 2.9 Å resolution, Science. 229: 1358–1365.PubMedCrossRefGoogle Scholar
  21. Kim, K.H., Willingmann, P., Gong, Z.X., Kremer, M.J., Chapman, M.S., Minor, I., Oliveira, M., Rossmann, M.G., Andries, K., Diana, G.D., Dutko, F.J., McKinlay, M.A. and Pevear, D.C., 1992, A Comparison of the Anti-rhinoviral Drug Binding Pocket in HRV14 and HRV1A, manuscript in preparation.Google Scholar
  22. Kim, S., Boege, U., Krishnaswamy, S., Minor, I., Smith, T.J., Luo, M., Scraba, D.G. and Rossmann, M.G., 1990, Conformational variability of a Picornavirus capsid: pH-dependent structural changes of Mengo virus related to its host receptor attachment site and disassembly, Virology. 175: 176–190.PubMedCrossRefGoogle Scholar
  23. Kim, S., Smith, T.J., Chapman, M.S., Rossmann, M.G., Pevear, D.C., Dutko, F.J., Felock, P.J., Diana, G.D. and McKinlay, M.A., 1989, The crystal structure of human rhinoviruses serotype 1A (HRVIA), J Mol Biol. 210: 91–111.PubMedCrossRefGoogle Scholar
  24. Klatzmann, D., Champagne, E., Chamaret, S., Gruest, J., Guetard, D., Hercend, T., Gluckman, J.-C. and Montagnier, L., 1984, T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV, Nature (London). 312: 767–768.CrossRefGoogle Scholar
  25. Koike, S., Ise, I. and Nomoto, A., 1991, Functional domains of the poliovirus receptor, Proc Natl Acad Sci USA. 88: 4104–4108.PubMedCrossRefGoogle Scholar
  26. Kolatkar, P.R., Oliveira, M.A., Rossmann, M.G., Robbins, A.H., Katti, S.K., Hooer-Litty, H., Forte, C., Greve, J.M., McClelland, A. and Olson, N.H., 1992, Preliminary X-ray crystallographic analysis of intercellular adhesion molecule-1, J Mol Biol., in press.Google Scholar
  27. Korant, B.D., Lonberg-Holm, K., Yin, F.H. and Noble-Harvey, J., 1975, Fractionation of biologically active and inactive populations of human rhinovirus type 2, Virology. 63: 384–394.PubMedCrossRefGoogle Scholar
  28. Kraulis, P.J., 1992, J Appl Crystallogr. 24: 946–950.CrossRefGoogle Scholar
  29. Lineberger, D.W., Graham, D.J., Tomassini, J.E. and Colonno, R.J., 1990, Antibodies that block rhinovirus attachment map to domain 1 of the major group receptor, J Virol. 64: 2582–2587.PubMedGoogle Scholar
  30. Maddon, P.J., Dalgleish, A.G., McDougal, J.S., Clapham, P.R., Weiss, R.A. and Axel, R., 1986, The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain, Cell. 47: 333–348.PubMedCrossRefGoogle Scholar
  31. Madshus, I.H., Olsnes, S. and Sandvig, K., 1984, Different pH requirements for entry of the two picornaviruses, human rhinovirus 2 and murine encephalomyocarditis virus, Virology. 139: 346–357.PubMedCrossRefGoogle Scholar
  32. Marlin, S.D., Staunton, D.E., Springer, T.A., Stratowa, C., Sommergruber, W. and Merluzzi, V.J., 1990, A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection, Nature (London). 344: 70–72.CrossRefGoogle Scholar
  33. McClelland, A., deBear, J., Yost, S.C., Meyer, A.M., Marlor, C.W. and Greve, J.M., 1991, Identification of monoclonal antibody epitopes and critical residues for rhinovirus binding in domain 1 of intercellular adhesion molecule 1, Proc Natl Acad Sci USA. 88: 7993–7997.PubMedCrossRefGoogle Scholar
  34. McKinlay, M.A., Pevear, D.C. and Rossmann, M.G., 1992, Treatment of the Picornavirus common cold by inhibitors of viral uncoating and attachment, Ann Rev Microbiol. manuscript in press.Google Scholar
  35. Mendelsohn, C.L., Wimmerm, E. and Racaniello, V.R., 1989, Cellular receptors for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily, Cell. 56: 855–865.PubMedCrossRefGoogle Scholar
  36. Minor, P.D., Ferguson, M., Katrak, K., Wood, D., John, A., Howlett, J., Dunn, G., Burke, K. and Almond, J.W., 1991, Antigenic structure of chimeras of type 1 and type 3 polioviruses involving antigenic sites 2, 3 and 4, J Gen Virol. 72: 2475–2481.PubMedCrossRefGoogle Scholar
  37. Pevear, D.C, Fancher, M.J., Felock, P.J., Rossmann, M.G., Miller, M.S., Diana, G., Treasurywala, A.M., McKinlay, M.A. and Dutko, F.J., 1989, Conformation change in the floor of the human rhinovirus canyon blocks adsorption to HeLa cell receptors, J Virol. 63:2002–2007.PubMedGoogle Scholar
  38. Prasad, B.V.V., Brurns, J.W., Marietta, E., Estes, M.K. and Chiu, W., 1990, Localization of VP4 neutralization sites in rotavirus by three-dimensional cryo-electron microscopy, Nature (London). 343: 476–479.CrossRefGoogle Scholar
  39. Register, R.B., Uncapher, C.R., Naylor, A.M., Lineberger, D.W. and Colonno, R.J., 1991, Human-murine chimeras of ICAM-1 identify amino acid residues critical for rhinovirus and antibody binding, J Virol. 65: 6589–6596.PubMedGoogle Scholar
  40. Robey, E. and Axel, R., 1990, CD4: collaborator in immune recognition and HIV infection, Cell. 60: 697–700.PubMedCrossRefGoogle Scholar
  41. Rossmann, M.G., 1989, Hiding the host cell receptor attachment site on a viral surface from immune surveillance, J Biol Chem. 263: 14587–14590.Google Scholar
  42. Rossmann, M.G. and Palmenberg, A.C., 1988, Conservation of the putative receptor attachment site in picornaviruses, Virology. 164: 373–382.PubMedCrossRefGoogle Scholar
  43. Rossmann, M.G., Arnold, E., Erickson, J.W., Frankenberger, E.A., Griffith, J.P., Hecht, H.J., Johnson, J.E., Kamer, G., Luo, M., Ruekert, A.G., Sherry, B. and Vriend, G., 1985, Structure of a human common cold virus and functional relationship to other picornaviruses, Nature (London). 317:145–153.CrossRefGoogle Scholar
  44. Ryu, S.E., Kwong, P.D., Truneh, A., Porter, T.G., Arthos, J., Rosenberg, M., Dai, X., Xuong, N., Axel, R., Sweet, R.W. and Hendrickson, W.A., 1990, Crystal structure of an HIV-binding recomginant fragment of human CD4, Nature (London). 348: 419–426.CrossRefGoogle Scholar
  45. Sauter, N.K., Glick, G.D., Crowther, R.L., Park, S.J., Eisen, M.B., Skehel, J.J., Knowles, J.R. and Wiley, D.C., 1992, Crystallographic detection of a second ligand binding site in influenza virus hemagglutinin, Proc Natl Acad Sci USA. 89: 324–328.PubMedCrossRefGoogle Scholar
  46. Sherry, B. and Rueckert, R., 1985, Evidence for at least two dominant neutralization antigens on human rhinovirus 14, J Virol. 53: 137–143.PubMedGoogle Scholar
  47. Sherry, B., Mosser, A.G., Colonno, R.J. and Rueckert, R.R., 1986, Use of monoclonal antibodies to identify four neutralization immunogens on a common cold Picornavirus, human rhinovirus 14, J Virol. 57: 246–257.PubMedGoogle Scholar
  48. Simmons, D., Makgoba, M.W. and Seed, B., 1988, ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM, Nature (London). 331: 624–627.CrossRefGoogle Scholar
  49. Siu, G., Hedrick, S.M. and Bian, A.A., 1989, Isolation of the murine intercellular adhesion molecule 1 (ICAM-1) gene, J Immunol. 143: 3813–3820.PubMedGoogle Scholar
  50. Smith, T.J., Kremer, M.J., Luo, M., Vriend, G., Arnold, E., Kamer, G., Rossmann, M.G., McKinlay, M.A., Diana, G.D. and Otto, M.J.,1986, The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating, Science. 233: 1286–1293.PubMedCrossRefGoogle Scholar
  51. Smith, T.J., Olson, N.H., Cheng, R.H., Chase, E., Lee, W.M., Leippe, D., Mosser, A., Rueckert, R.R. and Baker, T.S., 1992, Structure of human rhinovirus complexed with Fab fragments from a neutralizing antibody, Nature (London). Manuscript submitted for publication.Google Scholar
  52. Staunton, D.E., Dustin, M.L., Erickson, H.P. and Springer, T.A., 1990, The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding site for LFA-1 and rhinovirus, Cell, 61: 243–254.PubMedCrossRefGoogle Scholar
  53. Staunton, D.E., Marlin, S.D., Stratowa, C., Dustin, M.L., and Springer, T.A., 1988, Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families, Cell. 52: 925–933.PubMedCrossRefGoogle Scholar
  54. Staunton, D.E., Merluzzi, V.J., Rothlein, R., Barton, R., Marlin, S.D. and Springer, T.A., 1989, A cell adhesion molecule, ICAM-1, is the major suface receptor for rhinoviruses, Cell. 56: 849–853.PubMedCrossRefGoogle Scholar
  55. Tomassini, J.E., Maxson, T.R. and Colonno, R.J., 1989, Biochemical characterization of a glycoprotein required for rhinovirus attachment, J Biol Chem. 264:1656–1662.PubMedGoogle Scholar
  56. Toyoshima, C. and Unwin, N., 1988, Contrast transfer for frozen-hydrated specimens: determination from pairs of defocused images, Ultramicroscopy. 25: 279–282.PubMedCrossRefGoogle Scholar
  57. Uncapher, C.R., DeWitt, C.M. and Colonno, R.J., 1991, The major and minor group receptor families contain all but one human rhinovirus serotype, Virology. 180: 814–817.PubMedCrossRefGoogle Scholar
  58. Wang, G., Porta, C., Chen, Z., Baker, T.S. and Johnson, J.E., 1992, Identification of a Fab interaction footprint site on an icosahedral virus by cryoelectron microscopy and X-ray crystallography, Nature (London). 355: 275–278.CrossRefGoogle Scholar
  59. Wang, J., Yan, Y., Garret, T.P.J., Liu, J., Rodgers, D.W., Garlick, R.L., Tarr, G.E., Husain, Y., Reinherz, E.L. and Harrison, S.C., 1990, Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains, Nature (London). 348: 411–418.CrossRefGoogle Scholar
  60. Weis, W., Brown, J.H., Cusack, S., Paulson, J.C., Skehel, J.J. and Wiley, D.C., 1988, Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid, Nature (London), 333: 426–431.CrossRefGoogle Scholar
  61. Williams, R.K., Jiang, G.S. and Holmes, K.V., 1991, Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins, Proc Natl Acad Sci USA. 88: 5533–5536.PubMedCrossRefGoogle Scholar
  62. Yeates, T.O., Jacobson, D.H., Margin, A., Wychowki, C., Girard, M., Filman, D.J. and Hogle, J. M., 1991, Three-dimensional structure of a mouse-adapted type 2/type 1 poliovirus chimera, EMBO J. 10: 2331–2341.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Norman H. Olson
    • 1
  • Prasanna R. Kolatkar
    • 1
  • Marcos A. Oliveira
    • 1
  • R. Holland Cheng
    • 1
  • Jeffrey M. Greve
    • 2
  • Alan McClelland
    • 2
  • Timothy S. Baker
    • 1
  • Michael G. Rossmann
    • 1
  1. 1.Department of Biological SciencesPurdue UniversityWest LafayetteUSA
  2. 2.Institute for Molecular BiologicalsMiles INC.West HavenUSA

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