Human immunoglobulin E flexes between acutely bent and extended conformations

DOI: 10.1038/nsmb.2795
PMID: 24632569

Authors: Nyssa Drinkwater (Randall Division of Cell and Molecular Biophysics, King's College London) , Benjamin P Cossins (UCB Pharma) , Anthony H Keeble (Randall Division of Cell and Molecular Biophysics, King's College London) , 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 (Randall Division of Cell and Molecular Biophysics, King's College London) , James M Mcdonnell (Randall Division of Cell and Molecular Biophysics, King's College London) , Andrew J Beavil (Randall Division of Cell and Molecular Biophysics, King's College London) , Alistair J Henry (UCB Pharma) , Brian J J Sutton (Randall Division of Cell and Molecular Biophysics, King's College London)
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


Instruments: I03-Macromolecular Crystallography

Added On: 24/02/2015 10:36

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