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PDBsum entry 3ay4
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Immune system
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PDB id
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3ay4
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PDB id:
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Immune system
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Title:
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Crystal structure of nonfucosylated fc complexed with bis-glycosylated soluble form of fc gamma receptor iiia
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Structure:
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Ig gamma-1 chain c region. Chain: a, b. Fragment: fc fragment. Synonym: igg1. Engineered: yes. Low affinity immunoglobulin gamma fc region receptor iii-a. Chain: c. Fragment: extracellular domain. Engineered: yes.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ighg1. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Gene: fcgr3a.
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Resolution:
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2.20Å
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R-factor:
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0.225
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R-free:
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0.263
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Authors:
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T.Mizushima,E.Takemoto,H.Yagi,M.Shibata-Koyama,Y.Isoda,S.Iida, M.Satoh,K.Kato
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Key ref:
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T.Mizushima
et al.
(2011).
Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans.
Genes Cells,
16,
1071-1080.
PubMed id:
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Date:
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28-Apr-11
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Release date:
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03-Aug-11
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PROCHECK
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Headers
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References
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Genes Cells
16:1071-1080
(2011)
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PubMed id:
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Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans.
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T.Mizushima,
H.Yagi,
E.Takemoto,
M.Shibata-Koyama,
Y.Isoda,
S.Iida,
K.Masuda,
M.Satoh,
K.Kato.
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ABSTRACT
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Removal of the fucose residue from the N-glycans of the Fc portion of
immunoglobulin G (IgG) results in a dramatic enhancement of antibody-dependent
cellular cytotoxicity (ADCC) through improved affinity for Fcγ receptor IIIa
(FcγRIIIa). Here, we present the 2.2-Å structure of the complex formed between
nonfucosylated IgG1-Fc and a soluble form of FcγRIIIa (sFcγRIIIa) with two
N-glycosylation sites. The crystal structure shows that one of the two N-glycans
of sFcγRIIIa mediates the interaction with nonfucosylated Fc, thereby
stabilizing the complex. However, fucosylation of the Fc N-glycans inhibits this
interaction, because of steric hindrance, and furthermore, negatively affects
the dynamics of the receptor binding site. Our results offer a structural basis
for improvement in ADCC of therapeutic antibodies by defucosylation.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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I.Schwab,
and
F.Nimmerjahn
(2013).
Intravenous immunoglobulin therapy: how does IgG modulate the immune system?
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Nat Rev Immunol,
13,
176-189.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
