5MOL

Human IgE-Fc crystal structure


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.197 

wwPDB Validation 3D Report Full Report


This is version 1.0 of the entry. See complete history

Literature

Thermal sensitivity and flexibility of the C epsilon 3 domains in immunoglobulin E.

Dore, K.A.Davies, A.M.Drinkwater, N.Beavil, A.J.McDonnell, J.M.Sutton, B.J.

(2017) Biochim. Biophys. Acta 1865: 1336-1347

  • DOI: 10.1016/j.bbapap.2017.08.005
  • Primary Citation of Related Structures:  

  • PubMed Abstract: 
  • Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma. Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 a ...

    Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma. Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains. A sub-fragment lacking the Cε2 domains, Fcε3-4, also binds to both receptors, although receptor binding almost exclusively involves the Cε3 domains. This domain also contains the N-linked glycosylation site conserved in other isotypes. We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains. Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc. Intriguingly, both well-ordered carbohydrate and disordered polypeptide can be seen within the same Cε3 domain. A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states. Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.


    Organizational Affiliation

    King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, London SE1 1UL, United Kingdom; Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom. Electronic address: brian.sutton@kcl.ac.uk.,King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, London SE1 1UL, United Kingdom; Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Ig epsilon chain C region
A, B
327Homo sapiensMutation(s): 0 
Gene Names: IGHE
Find proteins for P01854 (Homo sapiens)
Go to UniProtKB:  P01854
Small Molecules
Ligands 7 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
MAN
Query on MAN

Download SDF File 
Download CCD File 
A, B
ALPHA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-PQMKYFCFSA-N
 Ligand Interaction
EDO
Query on EDO

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Download CCD File 
A, B
1,2-ETHANEDIOL
ETHYLENE GLYCOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
 Ligand Interaction
BMA
Query on BMA

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Download CCD File 
A, B
BETA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-RWOPYEJCSA-N
 Ligand Interaction
PG0
Query on PG0

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Download CCD File 
A, B
2-(2-METHOXYETHOXY)ETHANOL
PEG 6000
C5 H12 O3
SBASXUCJHJRPEV-UHFFFAOYSA-N
 Ligand Interaction
AE3
Query on AE3

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Download CCD File 
B
2-(2-ETHOXYETHOXY)ETHANOL
C6 H14 O3
XXJWXESWEXIICW-UHFFFAOYSA-N
 Ligand Interaction
PEG
Query on PEG

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Download CCD File 
A, B
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
 Ligand Interaction
NAG
Query on NAG

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Download CCD File 
A, B
N-ACETYL-D-GLUCOSAMINE
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.197 
  • Space Group: P 21 21 2
Unit Cell:
Length (Å)Angle (°)
a = 130.674α = 90.00
b = 75.782β = 90.00
c = 79.817γ = 90.00
Software Package:
Software NamePurpose
DIALSdata reduction
PHASERphasing
PHENIXrefinement
Aimlessdata scaling

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomG1100090

Revision History 

  • Version 1.0: 2018-01-10
    Type: Initial release