6P4L

Bile salts alter the mouse norovirus capsid conformation; possible implications for cell attachment and immune evasion.

  • Classification: VIRUS
  • Organism(s): Murine norovirus 1
  • Expression System: Murine norovirus 1
  • Mutation(s): No 

  • Deposited: 2019-05-28 Released: 2019-08-07 
  • Deposition Author(s): Smith, T.J.
  • Funding Organization(s): National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)

Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Bile Salts Alter the Mouse Norovirus Capsid Conformation: Possible Implications for Cell Attachment and Immune Evasion.

Sherman, M.B.Williams, A.N.Smith, H.Q.Nelson, C.Wilen, C.B.Fremont, D.H.Virgin, H.W.Smith, T.J.

(2019) J Virol 93

  • DOI: https://doi.org/10.1128/JVI.00970-19
  • Primary Citation of Related Structures:  
    6P4J, 6P4K, 6P4L

  • PubMed Abstract: 

    Caliciviruses are single-stranded RNA viruses with 180 copies of capsid protein comprising the T=3 icosahedral capsids. The main capsid feature is a pronounced protruding (P) domain dimer formed by adjacent subunits on the icosahedral surface while the shell domain forms a tight icosahedral sphere around the genome. While the P domain in the crystal structure of human Norwalk virus (genotype I.1) was tightly associated with the shell surface, the cryo-electron microscopy (cryo-EM) structures of several members of the Caliciviridae family (mouse norovirus [MNV], rabbit hemorrhagic disease virus, and human norovirus genotype II.10) revealed a "floating" P domain that hovers above the shell by nearly 10 to 15 Å in physiological buffers. Since this unusual feature is shared among, and unique to, the Caliciviridae , it suggests an important biological role. Recently, we demonstrated that bile salts enhance cell attachment to the target cell and increase the intrinsic affinity between the P domain and receptor. Presented here are the cryo-EM structures of MNV-1 in the presence of bile salts (∼3 Å) and the receptor CD300lf (∼8 Å). Surprisingly, bile salts cause the rotation and contraction of the P domain onto the shell surface. This both stabilizes the P domain and appears to allow for a higher degree of saturation of receptor onto the virus. Together, these results suggest that, as the virus moves into the gut and the associated high concentrations of bile, the entire capsid face undergoes a conformational change to optimize receptor avidity while the P domain itself undergoes smaller conformational changes to improve receptor affinity. IMPORTANCE Mouse norovirus and several other members of the Caliciviridae have been shown to have a highly unusual structure with the receptor binding protruding (P) domain only loosely tethered to the main capsid shell. Recent studies demonstrated that bile salts enhance the intrinsic P domain/receptor affinity and is necessary for cell attachment. Presented here are the high-resolution cryo-EM structures of apo MNV, MNV/bile salt, and MNV/bile salt/receptor. Bile salts cause a 90° rotation and collapse of the P domain onto the shell surface that may increase the number of available receptor binding sites. Therefore, bile salts appear to be having several effects on MNV. Bile salts shift the structural equilibrium of the P domain toward a form that binds the receptor and away from one that binds antibody. They may also cause the entire P domain to optimize receptor binding while burying a number of potential epitopes.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein
A, B, C
541Murine norovirus 1Mutation(s): 0 
UniProt
Find proteins for Q2V8W4 (Norovirus (isolate Mouse/NoV/United States/MNV1/2002/GV))
Explore Q2V8W4 
Go to UniProtKB:  Q2V8W4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2V8W4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data

  • Released Date: 2019-08-07 
  • Deposition Author(s): Smith, T.J.

Funding OrganizationLocationGrant Number
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)United States1R01-AI141465

Revision History  (Full details and data files)

  • Version 1.0: 2019-08-07
    Type: Initial release
  • Version 1.1: 2019-09-25
    Changes: Data collection, Database references
  • Version 1.2: 2019-12-18
    Changes: Author supporting evidence, Other
  • Version 1.3: 2024-03-20
    Changes: Data collection, Database references, Derived calculations