6BLA

Structure of AMM01 Fab, an anti EBV gH/gL neutralizing antibody


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.167 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus.

Snijder, J.Ortego, M.S.Weidle, C.Stuart, A.B.Gray, M.D.McElrath, M.J.Pancera, M.Veesler, D.McGuire, A.T.

(2018) Immunity 48: 799-811.e9

  • DOI: https://doi.org/10.1016/j.immuni.2018.03.026
  • Primary Citation of Related Structures:  
    6BLA, 6C5V

  • PubMed Abstract: 

    Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have focused on the gp350 glycoprotein and remain unsuccessful. We isolated human antibodies recognizing the EBV fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. We determined a cryo-electron microscopy reconstruction of the gH/gL-gp42-AMMO1 complex and demonstrated that AMMO1 bound to a discontinuous epitope formed by both gH and gL at the Domain-I/Domain-II interface. Integrating structural, biochemical, and infectivity data, we propose that AMMO1 inhibits fusion of the viral and cellular membranes. This work identifies a crucial epitope that may aid in the design of next-generation subunit vaccines against this major public health burden.


  • Organizational Affiliation

    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
AMM01 Fab Heavy chainA [auth H]227Homo sapiensMutation(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
AMM01 Fab Light chainB [auth L]216Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2PE
Query on 2PE

Download Ideal Coordinates CCD File 
M [auth H]NONAETHYLENE GLYCOL
C18 H38 O10
YZUUTMGDONTGTN-UHFFFAOYSA-N
TRS
Query on TRS

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L [auth H]2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
PEG
Query on PEG

Download Ideal Coordinates CCD File 
D [auth H],
E [auth H],
F [auth H],
N [auth L]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H,
U [auth L]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth H]
G [auth H]
O [auth L]
P [auth L]
Q [auth L]
C [auth H],
G [auth H],
O [auth L],
P [auth L],
Q [auth L],
R [auth L],
S [auth L],
T [auth L]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
I [auth H]
J [auth H]
K [auth H]
V [auth L]
W [auth L]
I [auth H],
J [auth H],
K [auth H],
V [auth L],
W [auth L],
X [auth L]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
A [auth H]L-PEPTIDE LINKINGC5 H7 N O3GLN
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.167 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.893α = 90
b = 69.937β = 90
c = 136.313γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-04-25
    Type: Initial release
  • Version 1.1: 2019-11-13
    Changes: Other, Structure summary