Details

Autor(en) / Beteiligte

• Keown, Maura B.
• Ghirlando, Rodolfo
• Young, Robert J.
• Beavil, Andrew J.
• Owens, Raymond J.
• Perkins, Stephen J.
• Sutton, Brian J.
• Gould, Hannah J.

Titel

Hydrodynamic Studies of a Complex Between the Fc Fragment of Human IgE and a Soluble Fragment of the FcεRI α Chain

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1995-03, Vol.92 (6), p.1841-1845

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1995

Quelle

MEDLINE

Beschreibungen/Notizen

• The interaction between immunoglobulin E (IgE) and its high-affinity receptor FcεRI is central to allergic disease. The binding site for FcεRI lies in the third constant region domain of the ε heavy chain of IgE (Cε3). Identical epitopes on the two Cε3 domains in the IgE-Fc are predicted to be on opposite sides of the structure, and therefore each could bind independently to a receptor molecule. Titrations, however, reveal that the IgE-Fc forms an equimolar complex with a soluble fragment of the FcεRI α chain (sFcεRIα), and the molecular weight of the complex, as determined by sedimentation equilibrium, confirms this stoichiometry. The measured sedimentation coefficients of the two ligands are in good agreement with computed values for a compact IgE-Fc and an elongated sFcεRIα structure. The calculated sedimentation coefficients for possible models of a 1:1 complex lead to exclusion of all highly extended geometries for the complex. Possible explanations for the paradoxical stoichiometry of the IgE-Fc/sFcεRIα complex, in terms of the curved shape of IgE, a conformational change in IgE when the receptor binds, and steric interference between two molecules of FcεRI binding to identical sites, are discussed.