6EYO

Structure of extended IgE-Fc in complex with two anti-IgE Fabs


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.70 Å
  • R-Value Free: 0.288 
  • R-Value Work: 0.247 
  • R-Value Observed: 0.250 

wwPDB Validation   3D Report Full Report



Literature

Structural basis for selective inhibition of immunoglobulin E-receptor interactions by an anti-IgE antibody.

Chen, J.B.Ramadani, F.Pang, M.O.Y.Beavil, R.L.Holdom, M.D.Mitropoulou, A.N.Beavil, A.J.Gould, H.J.Chang, T.W.Sutton, B.J.McDonnell, J.M.Davies, A.M.

(2018) Sci Rep 8: 11548-11548

  • DOI: 10.1038/s41598-018-29664-4
  • Primary Citation of Related Structures:  
    6EYO, 6EYN

  • PubMed Abstract: 
  • Immunoglobulin E (IgE) antibodies play a central role in the allergic response: interaction with FcεRI on mast cells and basophils leads to immediate hypersensitivity reactions upon allergen challenge, while interaction with CD23/FcεRII, expressed on ...

    Immunoglobulin E (IgE) antibodies play a central role in the allergic response: interaction with FcεRI on mast cells and basophils leads to immediate hypersensitivity reactions upon allergen challenge, while interaction with CD23/FcεRII, expressed on a variety of cells, regulates IgE synthesis among other activities. The receptor-binding IgE-Fc region has recently been found to display remarkable flexibility, from acutely bent to extended conformations, with allosteric communication between the distant FcεRI and CD23 binding sites. We report the structure of an anti-IgE antibody Fab (8D6) bound to IgE-Fc through a mixed protein-carbohydrate epitope, revealing further flexibility and a novel extended conformation with potential relevance to that of membrane-bound IgE in the B cell receptor for antigen. Unlike the earlier, clinically approved anti-IgE antibody omalizumab, 8D6 inhibits binding to FcεRI but not CD23; the structure reveals how this discrimination is achieved through both orthosteric and allosteric mechanisms, supporting therapeutic strategies that retain the benefits of CD23 binding.


    Organizational Affiliation

    Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom. anna.davies@kcl.ac.uk.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Immunoglobulin heavy constant epsilonAB327Homo sapiensMutation(s): 0 
Gene Names: IGHE
Find proteins for P01854 (Homo sapiens)
Explore P01854 
Go to UniProtKB:  P01854
NIH Common Fund Data Resources
PHAROS  P01854
Protein Feature View
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 2
MoleculeChainsSequence LengthOrganismDetailsImage
8D6 Fab heavy chainHI227Homo sapiensMutation(s): 0 
Protein Feature View
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 3
MoleculeChainsSequence LengthOrganismDetailsImage
8D6 Fab light chainLM218Homo sapiensMutation(s): 0 
Protein Feature View
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 4
MoleculeChainsChain Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
7 N-Glycosylation Oligosaccharides Interaction
Entity ID: 5
MoleculeChainsChain Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
6 N-Glycosylation Oligosaccharides Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.70 Å
  • R-Value Free: 0.288 
  • R-Value Work: 0.247 
  • R-Value Observed: 0.250 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 119.483α = 90
b = 119.601β = 90
c = 132.994γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomG1100090
Asthma UKUnited KingdomAUK-PG-2013-183
Wellcome TrustUnited Kingdom085944

Revision History 

  • Version 1.0: 2018-08-15
    Type: Initial release
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary