title: Human immunoglobulin E flexes between acutely bent and extended conformations.
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.
authors.affiliation: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.|Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
authors.forename: Nyssa
authors.initials: N
authors.lastname: Drinkwater
authors.affiliation: UCB Pharma, Slough, SL1 3WE, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Cossins
authors.affiliation: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.|Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Keeble
authors.affiliation: UCB Pharma, Slough, SL1 3WE, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Wright
authors.affiliation: UCB Pharma, Slough, SL1 3WE, UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Cain
authors.affiliation: UCB Pharma, Slough, SL1 3WE, UK.
authors.forename: Hanna
authors.initials: H
authors.lastname: Hailu
authors.affiliation: UCB Pharma, Slough, SL1 3WE, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Oxbrow
authors.affiliation: UCB Pharma, Slough, SL1 3WE, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Delgado
authors.affiliation: UCB Pharma, Slough, SL1 3WE, UK.
authors.forename: Lindsay K
authors.initials: LK
authors.lastname: Shuttleworth
authors.affiliation: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.|Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
authors.forename: Michael W-P
authors.initials: MW
authors.lastname: Kao
authors.affiliation: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.|Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: McDonnell
authors.affiliation: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.|Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Beavil
authors.affiliation: UCB Pharma, Slough, SL1 3WE, UK.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Henry
authors.affiliation: King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.|Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sutton
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D002151:Calorimetry; D018360:Crystallography, X-Ray; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017455:Receptors, IgE / Q000737:chemistry; D020349:Surface Plasmon Resonance
chemical_list: D017455:Receptors, IgE; D007073:Immunoglobulin E