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 C?2 domain pair folded back onto the C?3-C?4 domains, but is the molecule exclusively bent or can the C?2 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.

SUBMITTER: Drinkwater N 

PROVIDER: S-EPMC3977038 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature