5VZR

Crystal Structure of MERS-CoV neutralizing antibody G4 Fab


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.

Pallesen, J.Wang, N.Corbett, K.S.Wrapp, D.Kirchdoerfer, R.N.Turner, H.L.Cottrell, C.A.Becker, M.M.Wang, L.Shi, W.Kong, W.P.Andres, E.L.Kettenbach, A.N.Denison, M.R.Chappell, J.D.Graham, B.S.Ward, A.B.McLellan, J.S.

(2017) Proc Natl Acad Sci U S A 114: E7348-E7357

  • DOI: https://doi.org/10.1073/pnas.1707304114
  • Primary Citation of Related Structures:  
    5VYH, 5VZR, 5W9H, 5W9I, 5W9J, 5W9K, 5W9L, 5W9M, 5W9N, 5W9O, 5W9P

  • PubMed Abstract: 

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
G4 antibody heavy chainA [auth H],
C [auth A]
233Mus musculusMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
G4 antibody light chainB [auth L],
D [auth B]
218Mus musculusMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GOL
Query on GOL

Download Ideal Coordinates CCD File 
E [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
A [auth H],
C [auth A]
L-PEPTIDE LINKINGC5 H7 N O3GLN
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.678α = 90
b = 88.759β = 90
c = 128.469γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
iMOSFLMdata reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01AI127521

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-30
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Database references
  • Version 1.2: 2017-09-27
    Changes: Author supporting evidence
  • Version 2.0: 2019-12-11
    Changes: Author supporting evidence, Polymer sequence
  • Version 2.1: 2023-10-04
    Changes: Data collection, Database references, Refinement description