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Human immunoglobulin E flexes between acutely bent and extended conformations
DOI:
10.1038/nsmb.2795
PMID:
24632569
Authors:
Nyssa
Drinkwater
(King's College London; Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma)
,
Benjamin P.
Cossins
(UCB Pharma)
,
Anthony H.
Keeble
(King's College London; Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma)
,
Michael
Wright
(UCB Pharma)
,
Katharine
Cain
(UCB Pharma)
,
Hanna
Hailu
(UCB Pharma)
,
Amanda
Oxbrow
(UCB Pharma)
,
Jean
Delgado
(UCB Pharma)
,
Lindsay K
Shuttleworth
(UCB Pharma)
,
Michael W.-P.
Kao
(King's College London; Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma)
,
James M.
Mcdonnell
(King's College London; Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma)
,
Andrew J.
Beavil
(King's College London; Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma)
,
Alistair J.
Henry
(UCB Pharma)
,
Brian J.
Sutton
(King's College London; Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma)
Co-authored by industrial partner:
Yes
Type:
Journal Paper
Journal:
Nature Structural & Molecular Biology
, VOL 21 (4)
, PAGES 397 - 404
State:
Published (Approved)
Published:
March 2014
Abstract: Crystallographic and solution studies have shown that IgE molecules are acutely bent in their Fc region. Crystal structures reveal the Cɛ2 domain pair folded back onto the Cɛ3-Cɛ4 domains, but is the molecule exclusively bent or can the Cɛ2 domains adopt extended conformations and even 'flip' from one side of the molecule to the other? We report the crystal structure of IgE-Fc captured in a fully extended, symmetrical conformation and show by molecular dynamics, calorimetry, stopped-flow kinetic, surface plasmon resonance (SPR) and Förster resonance energy transfer (FRET) analyses that the antibody can indeed adopt such extended conformations in solution. This diversity of conformational states available to IgE-Fc offers a new perspective on IgE function in allergen recognition, as part of the B-cell receptor and as a therapeutic target in allergic disease.
Journal Keywords: Calorimetry; Crystallography; X-Ray; Fluorescence; Humans; Hypersensitivity; Immunoglobulin; Protein; Tertiary; Receptors; IgE; Surface Plasmon Resonance
Subject Areas:
Biology and Bio-materials,
Medicine
Instruments:
I03-Macromolecular Crystallography
Added On:
24/02/2015 10:36
Discipline Tags:
Health & Wellbeing
Structural biology
Drug Discovery
Life Sciences & Biotech
Allergic Diseases
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)