PMID- 22815482
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20220129
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 37
DP  - 2012 Sep 7
TI  - Mapping of the CD23 binding site on immunoglobulin E (IgE) and allosteric control 
      of the IgE-Fc epsilonRI interaction.
PG  - 31457-61
LID - 10.1074/jbc.C112.397059 [doi]
AB  - IgE, the antibody that mediates allergic responses, acts as part of a 
      self-regulating protein network. Its unique effector functions are controlled 
      through interactions of its Fc region with two cellular receptors, FcepsilonRI on mast 
      cells and basophils and CD23 on B cells. IgE cross-linked by allergen triggers 
      mast cell activation via FcepsilonRI, whereas IgE-CD23 interactions control IgE 
      expression levels. We have determined the CD23 binding site on IgE, using a 
      combination of NMR chemical shift mapping and site-directed mutagenesis. We show 
      that the CD23 and FcepsilonRI interaction sites are at opposite ends of the Cepsilon3 domain 
      of IgE, but that receptor binding is mutually inhibitory, mediated by an 
      allosteric mechanism. This prevents CD23-mediated cross-linking of IgE bound to 
      FcepsilonRI on mast cells and resulting antigen-independent anaphylaxis. The mutually 
      inhibitory nature of receptor binding provides a degree of autonomy for the 
      individual activities mediated by IgE-FcepsilonRI and IgE-CD23 interactions.
FAU - Borthakur, Susmita
AU  - Borthakur S
AD  - Randall Division of Cell and Molecular Biophysics, King's College London, Guy's 
      Campus, London SE1 1UL, United Kingdom.
FAU - Hibbert, Richard G
AU  - Hibbert RG
FAU - Pang, Marie O Y
AU  - Pang MO
FAU - Yahya, Norhakim
AU  - Yahya N
FAU - Bax, Heather J
AU  - Bax HJ
FAU - Kao, Michael W
AU  - Kao MW
FAU - Cooper, Alison M
AU  - Cooper AM
FAU - Beavil, Andrew J
AU  - Beavil AJ
FAU - Sutton, Brian J
AU  - Sutton BJ
FAU - Gould, Hannah J
AU  - Gould HJ
FAU - McDonnell, James M
AU  - McDonnell JM
LA  - eng
GR  - MR/J006742/1/MRC_/Medical Research Council/United Kingdom
GR  - G1000758/MRC_/Medical Research Council/United Kingdom
GR  - G0001352/MRC_/Medical Research Council/United Kingdom
GR  - G0400106/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120719
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Allosteric Regulation/immunology
MH  - Basophils/cytology/immunology/*metabolism
MH  - Cell Line
MH  - Humans
MH  - Immunoglobulin E/genetics/immunology/*metabolism
MH  - Mast Cells/cytology/immunology/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Peptide Mapping/methods
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Receptors, IgE/genetics/immunology/*metabolism
PMC - PMC3438978
EDAT- 2012/07/21 06:00
MHDA- 2012/12/10 06:00
PMCR- 2012/07/19
CRDT- 2012/07/21 06:00
PHST- 2012/07/21 06:00 [entrez]
PHST- 2012/07/21 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2012/07/19 00:00 [pmc-release]
AID - S0021-9258(20)63093-9 [pii]
AID - C112.397059 [pii]
AID - 10.1074/jbc.C112.397059 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Sep 7;287(37):31457-61. doi: 10.1074/jbc.C112.397059. Epub 2012 
      Jul 19.