6H2Y

human Fab 1E6 bound to fHbp variant 3 from Neisseria meningitidis serogroup B


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Cocrystal structure of meningococcal factor H binding protein variant 3 reveals a new crossprotective epitope recognized by human mAb 1E6.

Bianchi, F.Veggi, D.Santini, L.Buricchi, F.Bartolini, E.Lo Surdo, P.Martinelli, M.Finco, O.Masignani, V.Bottomley, M.J.Maione, D.Cozzi, R.

(2019) FASEB J 33: 12099-12111

  • DOI: https://doi.org/10.1096/fj.201900374R
  • Primary Citation of Related Structures:  
    6H2Y

  • PubMed Abstract: 

    The 4 component meningococcus B vaccine (4CMenB) vaccine is the first vaccine containing recombinant proteins licensed for the prevention of invasive meningococcal disease caused by meningococcal serogroup B strains. 4CMenB contains 3 main recombinant proteins, including the Neisseria meningitidis factor H binding protein (fHbp), a lipoprotein able to bind the human factor H. To date, over 1000 aa sequences of fHbp have been identified, and they can be divided into variant groups 1, 2, and 3, which are usually not crossprotective. Nevertheless, previous characterizations of a small set ( n = 10) of mAbs generated in humans after 4CMenB immunization revealed 2 human Fabs (huFabs) (1A12, 1G3) with some crossreactivity for variants 1, 2, and 3. This unexpected result prompted us to examine a much larger set of human mAbs ( n = 110), with the aim of better understanding the extent and nature of crossreactive anti-fHbp antibodies. In this study, we report an analysis of the human antibody response to fHbp, by the characterization of 110 huFabs collected from 3 adult vaccinees during a 6-mo study. Although the 4CMenB vaccine contains fHbp variant 1, 13 huFabs were also found to be crossreactive with variants 2 and 3. The crystal structure of the crossreactive huFab 1E6 in complex with fHbp variant 3 was determined, revealing a novel, highly conserved epitope distinct from the epitopes recognized by 1A12 or 1G3. Further, functional characterization shows that human mAb 1E6 is able to elicit rabbit, but not human, complement-mediated bactericidal activity against meningococci displaying fHbp from any of the 3 different variant groups. This functional and structural information about the human antibody response upon 4CMenB immunization contributes to further unraveling the immunogenic properties of fHbp. Knowledge gained about the epitope profile recognized by the human antibody repertoire could guide future vaccine design.-Bianchi, F., Veggi, D., Santini, L., Buricchi, F., Bartolini, E., Lo Surdo, P., Martinelli, M., Finco, O., Masignani, V., Bottomley, M. J., Maione, D., Cozzi, R. Cocrystal structure of meningococcal factor H binding protein variant 3 reveals a new crossprotective epitope recognized by human mAb 1E6.


  • Organizational Affiliation

    GlaxoSmithKline, Siena, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lipoprotein GNA1870A [auth D]275Neisseria meningitidisMutation(s): 0 
Gene Names: gna1870
UniProt
Find proteins for Q19KF7 (Neisseria meningitidis)
Explore Q19KF7 
Go to UniProtKB:  Q19KF7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ19KF7
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Heavy chainB [auth H]224Homo 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: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Light chainC [auth L]216Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
P33
Query on P33

Download Ideal Coordinates CCD File 
Q [auth L]3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL
C14 H30 O8
XPJRQAIZZQMSCM-UHFFFAOYSA-N
PG4
Query on PG4

Download Ideal Coordinates CCD File 
R [auth L]TETRAETHYLENE GLYCOL
C8 H18 O5
UWHCKJMYHZGTIT-UHFFFAOYSA-N
PEG
Query on PEG

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

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

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.208 
  • Space Group: P 2 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.979α = 90
b = 65.279β = 90
c = 278.828γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-08-14
    Type: Initial release
  • Version 1.1: 2020-02-26
    Changes: Database references