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J Virol. Aug 1994; 68(8): 5117–5125.
PMCID: PMC236455

Three-dimensional structure of baculovirus-expressed Norwalk virus capsids.


The three-dimensional structure of the baculovirus-expressed Norwalk virus capsid has been determined to a resolution of 2.2 nm using electron cryomicroscopy and computer image processing techniques. The empty capsid, 38.0 nm in diameter, exhibits T = 3 icosahedral symmetry and is composed of 90 dimers of the capsid protein. The striking features of the capsid structure are arch-like capsomeres, at the local and strict 2-fold axes, formed by dimers of the capsid protein and large hollows at the icosahedral 5- and 3-fold axes. Despite its distinctive architecture, the Norwalk virus capsid has several similarities with the structures of T = 3 single-stranded RNA (ssRNA) viruses. The structure of the protein subunit appears to be modular with three distinct domains: the distal globular domain (P2) that appears bilobed, a central stem domain (P1), and a lower shell domain (S). The distal domains of the 2-fold related subunits interact with each other to form the top of the arch. The lower domains of the adjacent subunits associate tightly to form a continuous shell between the radii of 11.0 and 15.0 nm. No significant mass density is observed below the radius of 11.0 mm. It is suspected that the hinge peptide in the adjoining region between the central domain and the shell domain may facilitate the subunits adapting to various quasi-equivalent environments. Architectural similarities between the Norwalk virus capsid and the other ssRNA viruses have suggested a possible domain organization along the primary sequence of the Norwalk virus capsid protein. It is suggested that the N-terminal 250 residues constitute the lower shell domain (S) with an eight-strand beta-barrel structure and that the C-terminal residues beyond 250 constitute the protruding (P1+P2) domains. A lack of an N-terminal basic region and the ability of the Norwalk virus capsid protein to form empty T = 3 shells suggest that the assembly pathway and the RNA packing mechanisms may be different from those proposed for tomato bushy stunt virus and southern bean mosaic virus but similar to that in tymoviruses and comoviruses.

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  • Acharya R, Fry E, Stuart D, Fox G, Rowlands D, Brown F. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature. 1989 Feb 23;337(6209):709–716. [PubMed]
  • Adrian M, Dubochet J, Lepault J, McDowall AW. Cryo-electron microscopy of viruses. Nature. 1984 Mar 1;308(5954):32–36. [PubMed]
  • Baker TS, Drak J, Bina M. Reconstruction of the three-dimensional structure of simian virus 40 and visualization of the chromatin core. Proc Natl Acad Sci U S A. 1988 Jan;85(2):422–426. [PMC free article] [PubMed]
  • Blacklow NR, Greenberg HB. Viral gastroenteritis. N Engl J Med. 1991 Jul 25;325(4):252–264. [PubMed]
  • CASPAR DL, KLUG A. Physical principles in the construction of regular viruses. Cold Spring Harb Symp Quant Biol. 1962;27:1–24. [PubMed]
  • Chen ZG, Stauffacher C, Li Y, Schmidt T, Bomu W, Kamer G, Shanks M, Lomonossoff G, Johnson JE. Protein-RNA interactions in an icosahedral virus at 3.0 A resolution. Science. 1989 Jul 14;245(4914):154–159. [PubMed]
  • Crowther RA. Procedures for three-dimensional reconstruction of spherical viruses by Fourier synthesis from electron micrographs. Philos Trans R Soc Lond B Biol Sci. 1971 May 27;261(837):221–230. [PubMed]
  • Dasgupta R, Kaesberg P. Complete nucleotide sequences of the coat protein messenger RNAs of brome mosaic virus and cowpea chlorotic mottle virus. Nucleic Acids Res. 1982 Jan 22;10(2):703–713. [PMC free article] [PubMed]
  • Dubochet J, Adrian M, Chang JJ, Homo JC, Lepault J, McDowall AW, Schultz P. Cryo-electron microscopy of vitrified specimens. Q Rev Biophys. 1988 May;21(2):129–228. [PubMed]
  • Fisher AJ, Johnson JE. Ordered duplex RNA controls capsid architecture in an icosahedral animal virus. Nature. 1993 Jan 14;361(6408):176–179. [PubMed]
  • Fuller SD. The T=4 envelope of Sindbis virus is organized by interactions with a complementary T=3 capsid. Cell. 1987 Mar 27;48(6):923–934. [PubMed]
  • Gray JJ, Jiang X, Morgan-Capner P, Desselberger U, Estes MK. Prevalence of antibodies to Norwalk virus in England: detection by enzyme-linked immunosorbent assay using baculovirus-expressed Norwalk virus capsid antigen. J Clin Microbiol. 1993 Apr;31(4):1022–1025. [PMC free article] [PubMed]
  • Green KY, Lew JF, Jiang X, Kapikian AZ, Estes MK. Comparison of the reactivities of baculovirus-expressed recombinant Norwalk virus capsid antigen with those of the native Norwalk virus antigen in serologic assays and some epidemiologic observations. J Clin Microbiol. 1993 Aug;31(8):2185–2191. [PMC free article] [PubMed]
  • Hogle JM, Chow M, Filman DJ. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. [PubMed]
  • Hogle JM, Maeda A, Harrison SC. Structure and assembly of turnip crinkle virus. I. X-ray crystallographic structure analysis at 3.2 A resolution. J Mol Biol. 1986 Oct 20;191(4):625–638. [PubMed]
  • Hosur MV, Schmidt T, Tucker RC, Johnson JE, Gallagher TM, Selling BH, Rueckert RR. Structure of an insect virus at 3.0 A resolution. Proteins. 1987;2(3):167–176. [PubMed]
  • Hyams KC, Malone JD, Kapikian AZ, Estes MK, Xi J, Bourgeois AL, Paparello S, Hawkins RE, Green KY. Norwalk virus infection among Desert Storm troops. J Infect Dis. 1993 Apr;167(4):986–987. [PubMed]
  • Xi JN, Graham DY, Wang KN, Estes MK. Norwalk virus genome cloning and characterization. Science. 1990 Dec 14;250(4987):1580–1583. [PubMed]
  • Jiang X, Wang M, Graham DY, Estes MK. Expression, self-assembly, and antigenicity of the Norwalk virus capsid protein. J Virol. 1992 Nov;66(11):6527–6532. [PMC free article] [PubMed]
  • Jiang X, Wang M, Wang K, Estes MK. Sequence and genomic organization of Norwalk virus. Virology. 1993 Jul;195(1):51–61. [PubMed]
  • Kaplan JE, Gary GW, Baron RC, Singh N, Schonberger LB, Feldman R, Greenberg HB. Epidemiology of Norwalk gastroenteritis and the role of Norwalk virus in outbreaks of acute nonbacterial gastroenteritis. Ann Intern Med. 1982 Jun;96(6 Pt 1):756–761. [PubMed]
  • Khan AS, Moe CL, Glass RI, Monroe SS, Estes MK, Chapman LE, Jiang X, Humphrey C, Pon E, Iskander JK, et al. Norwalk virus-associated gastroenteritis traced to ice consumption aboard a cruise ship in Hawaii: comparison and application of molecular method-based assays. J Clin Microbiol. 1994 Feb;32(2):318–322. [PMC free article] [PubMed]
  • Klug A, Finch JT. Structure of viruses of the papilloma-polyoma type. IV. Analysis of tilting experiments in the electron microscope. J Mol Biol. 1968 Jan 14;31(1):1–12. [PubMed]
  • Lew JF, Petric M, Kapikian AZ, Jiang X, Estes MK, Green KY. Identification of minireovirus as a Norwalk-like virus in pediatric patients with gastroenteritis. J Virol. 1994 May;68(5):3391–3396. [PMC free article] [PubMed]
  • Liljas L, Unge T, Jones TA, Fridborg K, Lövgren S, Skoglund U, Strandberg B. Structure of satellite tobacco necrosis virus at 3.0 A resolution. J Mol Biol. 1982 Jul 25;159(1):93–108. [PubMed]
  • Luo M, Vriend G, Kamer G, Minor I, Arnold E, Rossmann MG, Boege U, Scraba DG, Duke GM, Palmenberg AC. The atomic structure of Mengo virus at 3.0 A resolution. Science. 1987 Jan 9;235(4785):182–191. [PubMed]
  • Meyers G, Wirblich C, Thiel HJ. Genomic and subgenomic RNAs of rabbit hemorrhagic disease virus are both protein-linked and packaged into particles. Virology. 1991 Oct;184(2):677–686. [PubMed]
  • Neill JD. Nucleotide sequence of the capsid protein gene of two serotypes of San Miguel sea lion virus: identification of conserved and non-conserved amino acid sequences among calicivirus capsid proteins. Virus Res. 1992 Jul;24(2):211–222. [PubMed]
  • Neill JD, Reardon IM, Heinrikson RL. Nucleotide sequence and expression of the capsid protein gene of feline calicivirus. J Virol. 1991 Oct;65(10):5440–5447. [PMC free article] [PubMed]
  • Prasad BV, Burns JW, Marietta E, Estes MK, Chiu W. Localization of VP4 neutralization sites in rotavirus by three-dimensional cryo-electron microscopy. Nature. 1990 Feb 1;343(6257):476–479. [PubMed]
  • Prasad BV, Prevelige PE, Marietta E, Chen RO, Thomas D, King J, Chiu W. Three-dimensional transformation of capsids associated with genome packaging in a bacterial virus. J Mol Biol. 1993 May 5;231(1):65–74. [PubMed]
  • Prasad BV, Yamaguchi S, Roy P. Three-dimensional structure of single-shelled bluetongue virus. J Virol. 1992 Apr;66(4):2135–2142. [PMC free article] [PubMed]
  • Rossmann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht HJ, Johnson JE, Kamer G, Luo M, Mosser AG, et al. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. [PubMed]
  • Rossmann MG, Johnson JE. Icosahedral RNA virus structure. Annu Rev Biochem. 1989;58:533–573. [PubMed]
  • Sacher R, Ahlquist P. Effects of deletions in the N-terminal basic arm of brome mosaic virus coat protein on RNA packaging and systemic infection. J Virol. 1989 Nov;63(11):4545–4552. [PMC free article] [PubMed]
  • Sorger PK, Stockley PG, Harrison SC. Structure and assembly of turnip crinkle virus. II. Mechanism of reassembly in vitro. J Mol Biol. 1986 Oct 20;191(4):639–658. [PubMed]
  • Treanor JJ, Jiang X, Madore HP, Estes MK. Subclass-specific serum antibody responses to recombinant Norwalk virus capsid antigen (rNV) in adults infected with Norwalk, Snow Mountain, or Hawaii virus. J Clin Microbiol. 1993 Jun;31(6):1630–1634. [PMC free article] [PubMed]
  • Wei N, Morris TJ. Interactions between viral coat protein and a specific binding region on turnip crinkle virus RNA. J Mol Biol. 1991 Dec 5;222(3):437–443. [PubMed]

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