6DC4

RSV-neutralizing human antibody AM22

  • Classification: IMMUNE SYSTEM
  • Organism(s): Homo sapiens
  • Expression System: Homo sapiens
  • Mutation(s): No 

  • Deposited: 2018-05-04 Released: 2019-07-10 
  • Deposition Author(s): Jones, H.G., McLellan, J.S.
  • Funding Organization(s): National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Alternative conformations of a major antigenic site on RSV F.

Jones, H.G.Battles, M.B.Lin, C.C.Bianchi, S.Corti, D.McLellan, J.S.

(2019) PLoS Pathog 15: e1007944-e1007944

  • DOI: https://doi.org/10.1371/journal.ppat.1007944
  • Primary Citation of Related Structures:  
    6DC3, 6DC4, 6DC5

  • PubMed Abstract: 

    The respiratory syncytial virus (RSV) fusion (F) glycoprotein is a major target of neutralizing antibodies arising from natural infection, and antibodies that specifically bind to the prefusion conformation of RSV F generally demonstrate the greatest neutralization potency. Prefusion-stabilized RSV F variants have been engineered as vaccine antigens, but crystal structures of these variants have revealed conformational differences in a key antigenic site located at the apex of the trimer, referred to as antigenic site Ø. Currently, it is unclear if flexibility in this region is an inherent property of prefusion RSV F or if it is related to inadequate stabilization of site Ø in the engineered variants. Therefore, we set out to investigate the conformational flexibility of antigenic site Ø, as well as the ability of the human immune system to recognize alternative conformations of this site, by determining crystal structures of prefusion RSV F bound to neutralizing human-derived antibodies AM22 and RSD5. Both antibodies bound with high affinity and were specific for the prefusion conformation of RSV F. Crystal structures of the complexes revealed that the antibodies recognized distinct conformations of antigenic site Ø, each diverging at a conserved proline residue located in the middle of an α-helix. These data suggest that antigenic site Ø exists as an ensemble of conformations, with individual antibodies recognizing discrete states. Collectively, these results have implications for the refolding of pneumovirus and paramyxovirus fusion proteins and should inform development of prefusion-stabilized RSV F vaccine candidates.


  • Organizational Affiliation

    Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fab AM22 Heavy ChainA [auth H]228Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q6GMX6 (Homo sapiens)
Explore Q6GMX6 
Go to UniProtKB:  Q6GMX6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6GMX6
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Fab AM22 Light ChainB [auth L]215Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q8TCD0 (Homo sapiens)
Explore Q8TCD0 
Go to UniProtKB:  Q8TCD0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8TCD0
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth H]
D [auth H]
E [auth H]
F [auth H]
G [auth H]
C [auth H],
D [auth H],
E [auth H],
F [auth H],
G [auth H],
H,
I [auth H],
J [auth H],
K [auth H],
L [auth H],
M [auth L],
N [auth L],
O [auth L],
P [auth L],
Q [auth L],
R [auth L],
S [auth L]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.181 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.24α = 90
b = 75.22β = 90
c = 109.01γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
Aimlessdata scaling
PHASERphasing
PHENIXrefinement

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesP20GM113132

Revision History  (Full details and data files)

  • Version 1.0: 2019-07-10
    Type: Initial release
  • Version 1.1: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.2: 2020-01-22
    Changes: Database references
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description