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PDBsum entry 2dts
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Immune system
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PDB id
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2dts
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References listed in PDB file
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Key reference
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Title
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Structural comparison of fucosylated and nonfucosylated fc fragments of human immunoglobulin g1.
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Authors
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S.Matsumiya,
Y.Yamaguchi,
J.Saito,
M.Nagano,
H.Sasakawa,
S.Otaki,
M.Satoh,
K.Shitara,
K.Kato.
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Ref.
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J Mol Biol, 2007,
368,
767-779.
[DOI no: ]
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PubMed id
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Abstract
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Removal of the fucose residue from the oligosaccharides attached to Asn297 of
human immunoglobulin G1 (IgG1) results in a significant enhancement of
antibody-dependent cellular cytotoxicity (ADCC) via improved IgG1 binding to
Fcgamma receptor IIIa. To provide structural insight into the mechanisms of
affinity enhancement, we determined the crystal structure of the nonfucosylated
Fc fragment and compared it with that of fucosylated Fc. The overall
conformations of the fucosylated and nonfucosylated Fc fragments were similar
except for hydration mode around Tyr296. Stable-isotope-assisted NMR analyses
confirmed the similarity of the overall structures between fucosylated and
nonfucosylated Fc fragments in solution. These data suggest that the
glycoform-dependent ADCC enhancement is attributed to a subtle conformational
alteration in a limited region of IgG1-Fc. Furthermore, the electron density
maps revealed that the traces between Asp280 and Asn297 of our fucosylated and
nonfucosylated Fc crystals were both different from that in previously reported
isomorphous Fc crystals.
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Figure 3.
Figure 3. Environment around Tyr296. Possible hydrogen bonds
are indicated by blue broken lines accompanied by interatomic
distance (Å). (a) Chain A of Fuc (+). (b) Chain A of Fuc
(−).
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Figure 7.
Figure 7. Interface between the C′/E loop of Fc and
FcγRIII. Intermolecular hydrogen bonds are shown by broken
lines. (a) Fc (magenta)–FcγRIII (red) complex (hexagonal
form, PDB ID: 1E4K). (b) Fc (blue)–FcγRIII (yellow) complex
(orthorhombic form, PDB ID: 1T83).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
368,
767-779)
copyright 2007.
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