6PZ8

MERS S0 trimer in complex with variable domain of antibody G2


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.19 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation 3D Report Full Report


This is version 1.0 of the entry. See complete history

Literature

Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD.

Wang, N.Rosen, O.Wang, L.Turner, H.L.Stevens, L.J.Corbett, K.S.Bowman, C.A.Pallesen, J.Shi, W.Zhang, Y.Leung, K.Kirchdoerfer, R.N.Becker, M.M.Denison, M.R.Chappell, J.D.Ward, A.B.Graham, B.S.McLellan, J.S.

(2019) Cell Rep 28: 3395-3405.e6

  • DOI: 10.1016/j.celrep.2019.08.052

  • PubMed Abstract: 
  • Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) p ...

    Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV.


    Organizational Affiliation

    Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.,Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.,Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.,Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: jmclellan@austin.utexas.edu.,Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.,Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
S protein
A, E, I
472Middle East respiratory syndrome-related coronavirusMutation(s): 0 
Gene Names: S
Find proteins for W5ZZF5 (Middle East respiratory syndrome-related coronavirus)
Go to UniProtKB:  W5ZZF5
Entity ID: 2
MoleculeChainsSequence LengthOrganismDetails
S protein
B, J, F
726Middle East respiratory syndrome-related coronavirusMutation(s): 0 
Gene Names: S
Find proteins for W6A090 (Middle East respiratory syndrome-related coronavirus)
Go to UniProtKB:  W6A090
Entity ID: 3
MoleculeChainsSequence LengthOrganismDetails
G2 heavy chain
H, C, D
229N/AMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Entity ID: 4
MoleculeChainsSequence LengthOrganismDetails
G2 light chain
L, G, K
218N/AMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Small Molecules
Ligands 3 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
MAN
Query on MAN

Download SDF File 
Download CCD File 
B, F, J
ALPHA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-PQMKYFCFSA-N
 Ligand Interaction
BMA
Query on BMA

Download SDF File 
Download CCD File 
B, F, J
BETA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-RWOPYEJCSA-N
 Ligand Interaction
NAG
Query on NAG

Download SDF File 
Download CCD File 
A, B, E, F, I, J
N-ACETYL-D-GLUCOSAMINE
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.19 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious DiseasesUnited StatesAI127521

Revision History 

  • Version 1.0: 2019-10-09
    Type: Initial release