The intrinsic flexibility of IgE and its role in binding FcɛRI

The interaction between IgE and its high affinity cellular receptor (FcɛRI) is an essential step in the development of allergic responses. Studies have identified the third constant domain of IgE (Cɛ3) as the receptor binding region. The Cɛ3 domain has unusual structural features; it was found to be a ‘molten globule’ structure in an isolated form, only assuming a well structured form upon binding to FcɛRI. The conformational flexibility intrinsic to the receptor binding portion of the molecule may be useful to IgE in allowing the large allosteric changes postulated to be required for FcɛRI engagement. If allosteric inhibitors can be developed then the dynamic properties of the Cɛ3 domain may provide opportunities for therapeutic intervention in allergic disorders.