PMID- 15199058
OWN - NLM
STAT- MEDLINE
DCOM- 20050215
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 34
DP  - 2004 Aug 20
TI  - The importance of Lys-352 of human immunoglobulin E in FcepsilonRII/CD23 
      recognition.
PG  - 35320-5
AB  - The interaction of immunoglobulin E (IgE) with its low affinity receptor 
      (FcepsilonRII/CD23) plays a central role in the initiation and regulation of type 
      I hypersensitivity responses. We have previously identified the importance of 
      amino acid residues in the A-B loop of the Cepsilon3 domain of human IgE and 
      implicated a region close to the glycosylation site at asparagine 371 as 
      contributing to IgE-CD23 interaction. These residues were now targeted by 
      site-directed mutagenesis. The IgE-CD23 interaction was assessed by 
      semiquantitative flow cytometry. Replacement of the entire Cepsilon3 A-B loop 
      (residues 341-356) with the homologous rat IgE sequence resulted in complete loss 
      of human CD23 recognition, as did replacement of residues 346-353, indicating 
      that class-specific effector residue(s) are contained within these eight amino 
      acids. Lysine 352 within the A-B loop was identified as contributing directly to 
      human CD23 interaction. Mutation to the rodent homologue glycine or glutamate 
      resulted in a significant reduction in binding compared with native IgE, whereas 
      conservative substitution with arginine effected a small, but statistically 
      significant, enhancement of CD23 binding. Mutation of the Cepsilon3 glycosylation 
      site at asparagine 371 to threonine or glutamine did not significantly affect 
      CD23 recognition. Our results yield new insights into the structural basis of the 
      hIgE-CD23 interaction and hold promise for the rational design of drugs that can 
      manipulate IgE-mediated regulation of the allergic response.
FAU - Sayers, Ian
AU  - Sayers I
AD  - Krebs Institute, Department of Molecular Biology and Biotechnology, University of 
      Sheffield, Sheffield S10 2TN, United Kingdom.
FAU - Housden, Jonathan E M
AU  - Housden JE
FAU - Spivey, Alan C
AU  - Spivey AC
FAU - Helm, Birgit A
AU  - Helm BA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040615
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)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Drug Design
MH  - Humans
MH  - Immunoglobulin E/*genetics/metabolism
MH  - Lysine
MH  - Mutagenesis, Site-Directed
MH  - Protein Structure, Tertiary
MH  - Rats
MH  - Receptors, IgE/*metabolism
MH  - Structure-Activity Relationship
EDAT- 2004/06/17 05:00
MHDA- 2005/02/16 09:00
CRDT- 2004/06/17 05:00
PHST- 2004/06/17 05:00 [pubmed]
PHST- 2005/02/16 09:00 [medline]
PHST- 2004/06/17 05:00 [entrez]
AID - S0021-9258(20)73110-8 [pii]
AID - 10.1074/jbc.M404575200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Aug 20;279(34):35320-5. doi: 10.1074/jbc.M404575200. Epub 2004 
      Jun 15.