4J4P

The complex of human IgE-Fc with two bound Fab fragments

Summary for 4J4P

• Entry DOI: 10.2210/pdb4j4p/pdb
• Related: 1LSO 2WQR 2Y7Q
• Descriptor: Ig epsilon chain C region, Immunoglobulin G Fab Fragment Heavy Chain, Immunoglobulin G Fab Fragment Light Chain, ... (5 entities in total)
• Functional Keywords: ig like domain, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 177746.06

Authors

Drinkwater, N.,Sutton, B.J. (deposition date: 2013-02-07, release date: 2014-03-12, Last modification date: 2024-11-06)

Primary citation

Drinkwater, N.,Cossins, B.P.,Keeble, A.H.,Wright, M.,Cain, K.,Hailu, H.,Oxbrow, A.,Delgado, J.,Shuttleworth, L.K.,Kao, M.W.,McDonnell, J.M.,Beavil, A.J.,Henry, A.J.,Sutton, B.J.
Human immunoglobulin E flexes between acutely bent and extended conformations.
Nat.Struct.Mol.Biol., 21:397-404, 2014

PubMed 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.

PubMed: 24632569
DOI: 10.1038/nsmb.2795

Experimental method

X-RAY DIFFRACTION (2.91 Å)