 |
PDBsum entry 3ay4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
3ay4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their fc glycans.
|
|
|
Authors
|
|
T.Mizushima,
H.Yagi,
E.Takemoto,
M.Shibata-Koyama,
Y.Isoda,
S.Iida,
K.Masuda,
M.Satoh,
K.Kato.
|
|
|
Ref.
|
|
Genes Cells, 2011,
16,
1071-1080.
|
|
|
PubMed id
|
|
|
|
|
Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
|
|
|
|
Abstract
|
|
|
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.
|
|
|
|
|
|
|
