Human immunoglobulin E flexes between acutely bent and extended conformations

Nyssa Drinkwater; Benjamin P Cossins; Anthony H Keeble; Michael J Wright; Katharine Cain; Hanna Hailu; Amanda Oxbrow; Jean Delgado; Lindsay K Shuttleworth; Michael W-P Kao; James M McDonnell; Andrew Beavil; Alistair J Henry; Brian J Sutton

doi:10.1038/nsmb.2795

Human immunoglobulin E flexes between acutely bent and extended conformations

Nyssa Drinkwater, Benjamin P Cossins, Anthony H Keeble, Michael J Wright, Katharine Cain, Hanna Hailu, Amanda Oxbrow, Jean Delgado, Lindsay K Shuttleworth, Michael W-P Kao, James M McDonnell, Andrew Beavil, Alistair J Henry, Brian J Sutton

Research output: Contribution to journal › Article › Research › peer-review

54 Citations (Scopus)

Abstract

Crystallographic and solution studies have shown that IgE molecules are acutely bent in their Fc region. Crystal structures reveal the Cvarepsilon2 domain pair folded back onto the Cvarepsilon3-Cvarepsilon4 domains, but is the molecule exclusively bent or can the Cvarepsilon2 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 Forster 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.

Original language	English
Pages (from-to)	397-404
Number of pages	8
Journal	Nature Structural & Molecular Biology
Volume	21
Issue number	4
DOIs	https://doi.org/10.1038/nsmb.2795
Publication status	Published - 16 Mar 2014
Externally published	Yes

Access to Document

10.1038/nsmb.2795

Cite this

Drinkwater, N., Cossins, B. P., Keeble, A. H., Wright, M. J., Cain, K., Hailu, H., Oxbrow, A., Delgado, J., Shuttleworth, L. K., Kao, M. W.-P., McDonnell, J. M., Beavil, A., Henry, A. J., & Sutton, B. J. (2014). Human immunoglobulin E flexes between acutely bent and extended conformations. Nature Structural & Molecular Biology, 21(4), 397-404. https://doi.org/10.1038/nsmb.2795

@article{691ff2687f074d54b21888c15e13d143,

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 Cvarepsilon2 domain pair folded back onto the Cvarepsilon3-Cvarepsilon4 domains, but is the molecule exclusively bent or can the Cvarepsilon2 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 Forster 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.",

author = "Nyssa Drinkwater and Cossins, {Benjamin P} and Keeble, {Anthony H} and Wright, {Michael J} and Katharine Cain and Hanna Hailu and Amanda Oxbrow and Jean Delgado and Shuttleworth, {Lindsay K} and Kao, {Michael W-P} and McDonnell, {James M} and Andrew Beavil and Henry, {Alistair J} and Sutton, {Brian J}",

year = "2014",

month = mar,

day = "16",

doi = "10.1038/nsmb.2795",

language = "English",

volume = "21",

pages = "397--404",

journal = "Nature Structural & Molecular Biology",

issn = "1545-9993",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - Human immunoglobulin E flexes between acutely bent and extended conformations

AU - Drinkwater, Nyssa

AU - Cossins, Benjamin P

AU - Keeble, Anthony H

AU - Wright, Michael J

AU - Cain, Katharine

AU - Hailu, Hanna

AU - Oxbrow, Amanda

AU - Delgado, Jean

AU - Shuttleworth, Lindsay K

AU - Kao, Michael W-P

AU - McDonnell, James M

AU - Beavil, Andrew

AU - Henry, Alistair J

AU - Sutton, Brian J

PY - 2014/3/16

Y1 - 2014/3/16

N2 - Crystallographic and solution studies have shown that IgE molecules are acutely bent in their Fc region. Crystal structures reveal the Cvarepsilon2 domain pair folded back onto the Cvarepsilon3-Cvarepsilon4 domains, but is the molecule exclusively bent or can the Cvarepsilon2 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 Forster 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.

AB - Crystallographic and solution studies have shown that IgE molecules are acutely bent in their Fc region. Crystal structures reveal the Cvarepsilon2 domain pair folded back onto the Cvarepsilon3-Cvarepsilon4 domains, but is the molecule exclusively bent or can the Cvarepsilon2 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 Forster 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/24632569

U2 - 10.1038/nsmb.2795

DO - 10.1038/nsmb.2795

M3 - Article

SN - 1545-9993

VL - 21

SP - 397

EP - 404

JO - Nature Structural & Molecular Biology

JF - Nature Structural & Molecular Biology

IS - 4

ER -

Human immunoglobulin E flexes between acutely bent and extended conformations

Abstract

Access to Document

Other files and links

Cite this