4EZM

Crystal structure of the human IgE-Fc(epsilon)3-4 bound to its B cell receptor derCD23

Summary for 4EZM

• Entry DOI: 10.2210/pdb4ezm/pdb
• Related: 1FP5 1T8C 1T8D 2H2R 2H2T 2WQR 3H9Y 3H9Z 3HA0
• Descriptor: Ig epsilon chain C region, Low affinity immunoglobulin epsilon Fc receptor, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: immunoglobulin fold lectin, antibody receptor, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type II membrane protein: P06734
• Total number of polymer chains: 12
• Total formula weight: 252336.04

Authors

Dhaliwal, B.,Yuan, D.,Sutton, B.J. (deposition date: 2012-05-03, release date: 2012-07-18, Last modification date: 2024-10-16)

Primary citation

Dhaliwal, B.,Yuan, D.,Pang, M.O.,Henry, A.J.,Cain, K.,Oxbrow, A.,Fabiane, S.M.,Beavil, A.J.,McDonnell, J.M.,Gould, H.J.,Sutton, B.J.
Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor Fc{varepsilon}RI.
Proc.Natl.Acad.Sci.USA, 109:12686-12691, 2012

PubMed Abstract: The role of IgE in allergic disease mechanisms is performed principally through its interactions with two receptors, FcεRI on mast cells and basophils, and CD23 (FcεRII) on B cells. The former mediates allergic hypersensitivity, the latter regulates IgE levels, and both receptors, also expressed on antigen-presenting cells, contribute to allergen uptake and presentation to the immune system. We have solved the crystal structure of the soluble lectin-like "head" domain of CD23 (derCD23) bound to a subfragment of IgE-Fc consisting of the dimer of Cε3 and Cε4 domains (Fcε3-4). One CD23 head binds to each heavy chain at the interface between the two domains, explaining the known 2:1 stoichiometry and suggesting mechanisms for cross-linking membrane-bound trimeric CD23 by IgE, or membrane IgE by soluble trimeric forms of CD23, both of which may contribute to the regulation of IgE synthesis by B cells. The two symmetrically located binding sites are distant from the single FcεRI binding site, which lies at the opposite ends of the Cε3 domains. Structural comparisons with both free IgE-Fc and its FcεRI complex reveal not only that the conformational changes in IgE-Fc required for CD23 binding are incompatible with FcεRI binding, but also that the converse is true. The two binding sites are allosterically linked. We demonstrate experimentally the reciprocal inhibition of CD23 and FcεRI binding in solution and suggest that the mutual exclusion of receptor binding allows IgE to function independently through its two receptors.

PubMed: 22802656
DOI: 10.1073/pnas.1207278109

Experimental method

X-RAY DIFFRACTION (3.1 Å)