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PDBsum entry 3rjd
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Immune system
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PDB id
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3rjd
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PDB id:
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Immune system
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Title:
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Crystal structure of fc ri and its implication to high affinity immunoglobulin g binding
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Structure:
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High affinity immunoglobulin gamma fc receptor i. Chain: a. Fragment: unp residues 21-282. Synonym: igg fc receptor i, fc-gamma ri, fcri, fc-gamma ria, fcgammaria. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: fcgr1a, fcg1, fcgr1, igfr1. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: chinese hamster ovary (cho)
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Resolution:
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2.65Å
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R-factor:
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0.250
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R-free:
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0.276
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Authors:
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J.Lu,P.D.Sun
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Key ref:
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J.Lu
et al.
(2011).
Crystal structure of Fcγ receptor I and its implication in high affinity γ-immunoglobulin binding.
J Biol Chem,
286,
40608-40613.
PubMed id:
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Date:
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15-Apr-11
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Release date:
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21-Sep-11
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PROCHECK
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Headers
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References
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P12314
(FCGR1_HUMAN) -
High affinity immunoglobulin gamma Fc receptor I from Homo sapiens
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Seq:
Struc:
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374 a.a.
257 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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J Biol Chem
286:40608-40613
(2011)
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PubMed id:
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Crystal structure of Fcγ receptor I and its implication in high affinity γ-immunoglobulin binding.
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J.Lu,
J.L.Ellsworth,
N.Hamacher,
S.W.Oak,
P.D.Sun.
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ABSTRACT
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Fcγ receptors (FcγRs) play critical roles in humoral and cellular immune
responses through interactions with the Fc region of immunoglobulin G (IgG).
Among them, FcγRI is the only high affinity receptor for IgG and thus is a
potential target for immunotherapy. Here we report the first crystal structure
of an FcγRI with all three extracellular Ig-like domains (designated as D1, D2,
and D3). The structure shows that, first, FcγRI has an acute D1-D2 hinge angle
similar to that of FcεRI but much smaller than those observed in the low
affinity Fcγ receptors. Second, the D3 domain of FcγRI is positioned away from
the putative IgG binding site on the receptor and is thus unlikely to make
direct contacts with Fc. Third, the replacement of FcγRIII FG-loop
((171)LVGSKNV(177)) with that of FcγRI ((171)MGKHRY(176)) resulted in a 15-fold
increase in IgG(1) binding affinity, whereas a valine insertion in the FcγRI
FG-loop ((171)MVGKHRY(177)) abolished the affinity enhancement. Thus, the FcγRI
FG-loop with its conserved one-residue deletion is critical to the high affinity
IgG binding. The structural results support FcγRI binding to IgG in a similar
mode as its low affinity counterparts. Taken together, our study suggests a
molecular mechanism for the high affinity IgG recognition by FcγRI and provides
a structural basis for understanding its physiological function and its
therapeutic implication in treating autoimmune diseases.
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Links
