Home LiteratureArticle Details
PMID: 14610179 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket.

Journal of virology ·Vol. 77 ·No. 23 ·2003-12-00 ·Pages 12562-71

Tan M, Huang P, Meller J, Zhong W, Farkas T, Jiang X

Abstract

Noroviruses (NORs) are an important cause of acute gastroenteritis. Recent studies of NOR receptors showed that different NORs bind to different histo-blood group antigens (HBGAs), and at least four distinct binding patterns were observed. To determine the structure-function relationship for NORs and their receptors, two strains representing two of the four binding patterns were studied. Strain VA387 binds to HBGAs of A, B, and O secretors, whereas strain MOH binds to HBGAs of A and B secretors only. Using multiple sequence alignments, homology modeling, and structural analysis of NOR capsids, we identified a plausible "pocket" in the P2 domain that may be responsible for binding to HBGA receptors. This pocket consists of a conserved RGD/K motif surrounded by three strain-specific hot spots (N(302), T(337), and Q(375) for VA387 and N(302), N(338), and E(378) for MOH). Subsequent mutagenesis experiments demonstrated that all four sites played important roles in binding. A single amino acid mutation at T(337) (to A) in VA387 or a double amino acid mutation at RN(338) (to TT) in MOH abolished binding completely. Change of the entire RGD motif to SAS abolished binding in case of VA387, whereas single amino acid mutations in that motif did not have an apparent effect on binding to A and B antigens but decreased binding to H antigen. Multiple mutations at the RGK motif of MOH (SIRGK to TFRGD) completely knocked out the binding. Mutation of N(302) or Q(375) in VA387 affected binding to type O HBGA only, while switch mutants with three amino acid changes at either site from MOH to VA387 resulted in a weak binding to type O HBGAs. A further switch mutant with three amino acid changes at E(378) from MOH to VA387 diminished the binding to type A HBGA only. Taken together, our data indicate that the binding pocket likely exists on NOR capsids. Direct evidence of this hypothesis requires crystallography studies.

MeSH Terms
Amino Acid Sequence Base Sequence Capsid Proteins/chemistry,genetics,metabolism DNA Primers HLA Antigens/metabolism Humans Microscopy, Electron Models, Molecular Molecular Sequence Data Mutation Norovirus/genetics Nucleolus Organizer Region Protein Binding Sequence Homology, Amino Acid
Chemicals
Capsid Proteins DNA Primers HLA Antigens
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Tan Ming
Division of Infectious Diseases and Division of Pediatric Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Huang Pengwei
Meller Jaroslaw
Zhong Weiming
Farkas Tibor
Jiang Xi
References (46)
46 references, click to expand
  1. Enhanced genome annotation using structural profiles in the program 3D-PSSM.
    J Mol Biol. 2000 Jun 2;299(2):499-520 PMID: 10860755
  2. X-ray crystallographic structure of the Norwalk virus capsid.
    Science. 1999 Oct 8;286(5438):287-90 PMID: 10514371
  3. Capsid protein diversity among Norwalk-like viruses.
    Virus Genes. 2000;20(3):227-36 PMID: 10949950
  4. Pathogenesis of urinary tract infections: an update.
    J Antimicrob Chemother. 2000 Sep;46 Suppl 1:1-7; discussion 63-5 PMID: 11051617
  5. Binding of rabbit hemorrhagic disease virus to antigens of the ABH histo-blood group family.
    J Virol. 2000 Dec;74(24):11950-4 PMID: 11090195
  6. ABH and Lewis histo-blood group antigens, a model for the meaning of oligosaccharide diversity in the face of a changing world.
    Biochimie. 2001 Jul;83(7):565-73 PMID: 11522384
  7. Linear programming optimization and a double statistical filter for protein threading protocols.
    Proteins. 2001 Nov 15;45(3):241-61 PMID: 11599028
  8. Baculovirus expression and antigenic characterization of the capsid proteins of three Norwalk-like viruses.
    Arch Virol. 2002;147(1):119-30 PMID: 11855626
  9. Structural requirements for the assembly of Norwalk virus-like particles.
    J Virol. 2002 Apr;76(8):4044-55 PMID: 11907243
  10. Norwalk virus infection and disease is associated with ABO histo-blood group type.
    J Infect Dis. 2002 May 1;185(9):1335-7 PMID: 12001052
  11. Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals.
    Gastroenterology. 2002 Jun;122(7):1967-77 PMID: 12055602
  12. Epidemiologic and molecular trends of "Norwalk-like viruses" associated with outbreaks of gastroenteritis in the United States.
    J Infect Dis. 2002 Jul 1;186(1):1-7 PMID: 12089655
  13. Molecular detection and sequence analysis of human caliciviruses from acute gastroenteritis outbreaks in Hungary.
    J Med Virol. 2002 Aug;67(4):567-73 PMID: 12116006
  14. Viruses detected in the caecum contents of healthy pigs representing a new genetic cluster in genogroup II of the genus "Norwalk-like viruses".
    Virus Res. 2002 Aug;87(2):165-72 PMID: 12191780
  15. Foodborne viral gastroenteritis: challenges and opportunities.
    Clin Infect Dis. 2002 Sep 15;35(6):748-53 PMID: 12203173
  16. Binding of Norwalk virus-like particles to ABH histo-blood group antigens is blocked by antisera from infected human volunteers or experimentally vaccinated mice.
    J Virol. 2002 Dec;76(23):12335-43 PMID: 12414974
  17. Norwalk virus-like particle hemagglutination by binding to h histo-blood group antigens.
    J Virol. 2003 Jan;77(1):405-15 PMID: 12477845
  18. Molecular characterization of bovine enteric caliciviruses: a distinct third genogroup of noroviruses (Norwalk-like viruses) unlikely to be of risk to humans.
    J Virol. 2003 Feb;77(4):2789-98 PMID: 12552024
  19. Human susceptibility and resistance to Norwalk virus infection.
    Nat Med. 2003 May;9(5):548-53 PMID: 12692541
  20. Noroviruses bind to human ABO, Lewis, and secretor histo-blood group antigens: identification of 4 distinct strain-specific patterns.
    J Infect Dis. 2003 Jul 1;188(1):19-31 PMID: 12825167
  21. Predisposition for cholera of individuals with O blood group. Possible evolutionary significance.
    Am J Epidemiol. 1985 Jun;121(6):791-6 PMID: 4014172
  22. Arg-Gly-Asp: a versatile cell recognition signal.
    Cell. 1986 Feb 28;44(4):517-8 PMID: 2418980
  23. Secretor state and immunoglobulin levels among women with recurrent urinary tract infections.
    J Clin Lab Immunol. 1987 Mar;22(3):133-7 PMID: 3612749
  24. Blood group, secretor status and oral carriage of yeasts among patients with diabetes mellitus.
    Diabetes Res. 1989 Nov;12(3):101-4 PMID: 2699583
  25. Norwalk virus genome cloning and characterization.
    Science. 1990 Dec 14;250(4987):1580-3 PMID: 2177224
  26. Association between secretor status and respiratory viral illness.
    BMJ. 1991 Oct 5;303(6806):815-8 PMID: 1932971
  27. Blood group non-secretors have an increased inflammatory response to urinary tract infection.
    Scand J Infect Dis. 1992;24(1):77-83 PMID: 1589729
  28. Binding of uropathogenic Escherichia coli R45 to glycolipids extracted from vaginal epithelial cells is dependent on histo-blood group secretor status.
    J Clin Invest. 1992 Sep;90(3):965-72 PMID: 1522244
  29. Expression, self-assembly, and antigenicity of the Norwalk virus capsid protein.
    J Virol. 1992 Nov;66(11):6527-32 PMID: 1328679
  30. Sequence and genomic organization of Norwalk virus.
    Virology. 1993 Jul;195(1):51-61 PMID: 8391187
  31. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens.
    Science. 1993 Dec 17;262(5141):1892-5 PMID: 8018146
  32. RGD sequence of foot-and-mouth disease virus is essential for infecting cells via the natural receptor but can be bypassed by an antibody-dependent enhancement pathway.
    Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1932-6 PMID: 8127909
  33. Three-dimensional structure of baculovirus-expressed Norwalk virus capsids.
    J Virol. 1994 Aug;68(8):5117-25 PMID: 8035511
  34. Helicobacter pylori: molecular basis for host recognition and bacterial adherence.
    Trends Microbiol. 1994 Jul;2(7):221-8 PMID: 8081648
  35. Derivation of rules for comparative protein modeling from a database of protein structure alignments.
    Protein Sci. 1994 Sep;3(9):1582-96 PMID: 7833817
  36. Expression, self-assembly, and antigenicity of a snow mountain agent-like calicivirus capsid protein.
    J Clin Microbiol. 1995 Jun;33(6):1452-5 PMID: 7650166
  37. The relationship between gastric cancer frequency and the ratio of gastric to duodenal ulcer.
    Aliment Pharmacol Ther. 1995;9 Suppl 2:13-9 PMID: 8547523
  38. Influence of blood group and secretor status on carbohydrate structures in human gastric mucins: implications for peptic ulcer.
    Clin Sci (Lond). 1995 Oct;89(4):405-15 PMID: 7493441
  39. Targeting of adenovirus penton base to new receptors through replacement of its RGD motif with other receptor-specific peptide motifs.
    Gene Ther. 1995 Dec;2(10):750-6 PMID: 8750015
  40. Rotavirus contains integrin ligand sequences and a disintegrin-like domain that are implicated in virus entry into cells.
    Proc Natl Acad Sci U S A. 1997 May 13;94(10):5389-94 PMID: 9144247
  41. Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: a new homology modeling tool.
    J Mol Biol. 1997 Apr 18;267(5):1268-82 PMID: 9150411
  42. The Helicobacter pylori seroprevalence in blood donors related to Lewis (a,b) histo-blood group phenotype.
    Eur J Gastroenterol Hepatol. 1997 Apr;9(4):367-70 PMID: 9160199
  43. Biochemical characterization of a smaller form of recombinant Norwalk virus capsids assembled in insect cells.
    J Virol. 1997 Oct;71(10):8066-72 PMID: 9311906
  44. Computer simulations of carbon monoxide photodissociation in myoglobin: structural interpretation of the B states.
    Biophys J. 1998 Feb;74(2 Pt 1):789-802 PMID: 9533692
  45. The P histo-blood group-related glycosphingolipid sialosyl galactosyl globoside as a preferred binding receptor for uropathogenic Escherichia coli: isolation and structural characterization from human kidney.
    Biochemistry. 1998 Dec 15;37(50):17420-8 PMID: 9860857
  46. Molecular characterization of a bovine enteric calicivirus: relationship to the Norwalk-like viruses.
    J Virol. 1999 Jan;73(1):819-25 PMID: 9847396
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.77.23.12562-12571.2003
Published
2003-12-00
Pages
12562-71
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC262557
Subset
IM
Grants
NIAID NIH HHS · R01 AI037093 · United States
NIAID NIH HHS · R01 AI37093-6 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1128/jvi.77.23.12562-12571.2003 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2