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 1.1 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
  • Structures With Same Primary Citation

  • 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. Electronic address: jmclellan@austin.utexas.edu.



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 
Find proteins for K9N5Q8 (Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012))
Go to UniProtKB:  K9N5Q8

Find similar proteins by: Sequence  |  Structure

Entity ID: 2
MoleculeChainsSequence LengthOrganismDetails
S protein
B, F, J
726Middle East respiratory syndrome-related coronavirusMutation(s): 0 
Find proteins for K9N5Q8 (Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012))
Go to UniProtKB:  K9N5Q8

Find similar proteins by: Sequence  |  Structure

Entity ID: 3
MoleculeChainsSequence LengthOrganismDetails
G2 heavy chain
C, D, H
229Mus musculusMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.

Find similar proteins by: Sequence  |  Structure

Entity ID: 4
MoleculeChainsSequence LengthOrganismDetails
G2 light chain
G, K, L
218Mus musculusMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Small Molecules
Ligands 3 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download CCD File 
A, B, E, F, I, J
N-ACETYL-D-GLUCOSAMINE
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
BMA
Query on BMA

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

Download CCD File 
B, F, J
ALPHA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-PQMKYFCFSA-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



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI127521

Revision History 

  • Version 1.0: 2019-10-09
    Type: Initial release
  • Version 1.1: 2019-12-18
    Changes: Author supporting evidence