PMID- 16172256 OWN - NLM STAT- MEDLINE DCOM- 20051115 LR - 20220129 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 202 IP - 6 DP - 2005 Sep 19 TI - The structure of human CD23 and its interactions with IgE and CD21. PG - 751-60 AB - The low-affinity immunoglobulin E (IgE) receptor, CD23 (FcepsilonRII), binds both IgE and CD21 and, through these interactions, regulates the synthesis of IgE, the antibody isotype that mediates the allergic response. We have determined the three-dimensional structure of the C-type lectin domain of CD23 in solution by nuclear magnetic resonance spectroscopy. An analysis of concentration-dependent chemical shift perturbations have allowed us to identify the residues engaged in self-association to the trimeric state, whereas ligand-induced changes have defined the binding sites for IgE and CD21. The results further reveal that CD23 can bind both ligands simultaneously. Despite the C-type lectin domain structure, none of the interactions require calcium. We also find that IgE and CD23 can interact to form high molecular mass multimeric complexes. The interactions that we have described provide a solution to the paradox that CD23 is involved in both up- and down-regulation of IgE and provide a structural basis for the development of inhibitors of allergic disease. FAU - Hibbert, Richard G AU - Hibbert RG AD - Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK. FAU - Teriete, Peter AU - Teriete P FAU - Grundy, Gabrielle J AU - Grundy GJ FAU - Beavil, Rebecca L AU - Beavil RL FAU - Reljic, Rajko AU - Reljic R FAU - Holers, V Michael AU - Holers VM FAU - Hannan, Jonathan P AU - Hannan JP FAU - Sutton, Brian J AU - Sutton BJ FAU - Gould, Hannah J AU - Gould HJ FAU - McDonnell, James M AU - McDonnell JM LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - G0200486/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Lectins) RN - 0 (Ligands) RN - 0 (Receptors, Complement 3d) RN - 0 (Receptors, IgE) RN - 37341-29-0 (Immunoglobulin E) RN - SY7Q814VUP (Calcium) SB - IM MH - Binding Sites MH - Calcium/metabolism MH - Down-Regulation/immunology MH - Humans MH - Immunoglobulin E/biosynthesis/*metabolism MH - Lectins/physiology MH - Ligands MH - Magnetic Resonance Spectroscopy MH - Protein Binding MH - Protein Structure, Tertiary MH - Receptors, Complement 3d/*metabolism MH - Receptors, IgE/*chemistry/*metabolism MH - Surface Plasmon Resonance MH - Up-Regulation/immunology PMC - PMC2212946 EDAT- 2005/09/21 09:00 MHDA- 2005/11/16 09:00 PMCR- 2006/03/19 CRDT- 2005/09/21 09:00 PHST- 2005/09/21 09:00 [pubmed] PHST- 2005/11/16 09:00 [medline] PHST- 2005/09/21 09:00 [entrez] PHST- 2006/03/19 00:00 [pmc-release] AID - jem.20050811 [pii] AID - 20050811 [pii] AID - 10.1084/jem.20050811 [doi] PST - ppublish SO - J Exp Med. 2005 Sep 19;202(6):751-60. doi: 10.1084/jem.20050811.