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PDBsum entry 4g9a
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Immune system
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PDB id
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4g9a
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PDB id:
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| Name: |
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Immune system
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Title:
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Crystal structure of calcium2+-bound wild-type cd23 lectin domain
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Structure:
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Low affinity immunoglobulin epsilon fc receptor. Chain: a, b, c, d. Fragment: unp residues 156-298. Synonym: blast-2, c-type lectin domain family 4 member j, fc-epsilon- rii, immunoglobulin e-binding factor, lymphocyte ige receptor, low affinity immunoglobulin epsilon fc receptor membrane-bound form, low affinity immunoglobulin epsilon fc receptor soluble form. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: cd23a, clec4j, fce2, fcer2, igebf. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.00Å
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R-factor:
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0.155
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R-free:
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0.205
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Authors:
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D.Yuan,B.J.Sutton,B.Dhaliwal
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Key ref:
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D.Yuan
et al.
(2013).
Ca2+-dependent structural changes in the B-cell receptor CD23 increase its affinity for human immunoglobulin E.
J Biol Chem,
288,
21667-21677.
PubMed id:
DOI:
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Date:
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23-Jul-12
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Release date:
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26-Jun-13
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PROCHECK
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Headers
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References
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P06734
(FCER2_HUMAN) -
Low affinity immunoglobulin epsilon Fc receptor from Homo sapiens
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Seq:
Struc:
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321 a.a.
132 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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J Biol Chem
288:21667-21677
(2013)
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PubMed id:
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Ca2+-dependent structural changes in the B-cell receptor CD23 increase its affinity for human immunoglobulin E.
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D.Yuan,
A.H.Keeble,
R.G.Hibbert,
S.Fabiane,
H.J.Gould,
J.M.McDonnell,
A.J.Beavil,
B.J.Sutton,
B.Dhaliwal.
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ABSTRACT
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Immunoglobulin E (IgE) antibodies play a fundamental role in allergic disease
and are a target for therapeutic intervention. IgE functions principally through
two receptors, FcεRI and CD23 (FcεRII). Minute amounts of allergen trigger
mast cell or basophil degranulation by cross-linking IgE-bound FcεRI, leading
to an inflammatory response. The interaction between IgE and CD23 on B-cells
regulates IgE synthesis. CD23 is unique among Ig receptors in that it belongs to
the C-type (calcium-dependent) lectin-like superfamily. Although the interaction
of CD23 with IgE is carbohydrate-independent, calcium has been reported to
increase the affinity for IgE, but the structural basis for this activity has
previously been unknown. We have determined the crystal structures of the human
lectin-like head domain of CD23 in its Ca(2+)-free and Ca(2+)-bound forms, as
well as the crystal structure of the Ca(2+)-bound head domain of CD23 in complex
with a subfragment of IgE-Fc consisting of the dimer of Cε3 and Cε4 domains
(Fcε3-4). Together with site-directed mutagenesis, the crystal structures of
four Ca(2+) ligand mutants, isothermal titration calorimetry, surface plasmon
resonance, and stopped-flow analysis, we demonstrate that Ca(2+) binds at the
principal and evolutionarily conserved binding site in CD23. Ca(2+) binding
drives Pro-250, at the base of an IgE-binding loop (loop 4), from the trans to
the cis configuration with a concomitant conformational change and ordering of
residues in the loop. These Ca(2+)-induced structural changes in CD23 lead to
additional interactions with IgE, a more entropically favorable interaction, and
a 30-fold increase in affinity of a single head domain of CD23 for IgE. Taken
together, these results suggest that binding of Ca(2+) brings an extra degree of
modulation to CD23 function.
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Links
