2DTS

Crystal Structure of the Defucosylated Fc Fragment from Human Immunoglobulin G1

Summary for 2DTS

• Entry DOI: 10.2210/pdb2dts/pdb
• Related: 1E4K 1H3X 1HZH 1L6X 1T83 2DTQ
• Descriptor: Ig gamma-1 chain C region, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: immunoglobulin, igg1, defucosylated glycoform, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P01857
• Total number of polymer chains: 2
• Total formula weight: 52626.09

Authors

Matsumiya, S.,Yamaguchi, Y.,Saito, J.,Nagano, M.,Sasakawa, H.,Otaki, S.,Satoh, M.,Shitara, K.,Kato, K. (deposition date: 2006-07-14, release date: 2007-03-13, Last modification date: 2023-10-25)

Primary citation

Matsumiya, S.,Yamaguchi, Y.,Saito, J.,Nagano, M.,Sasakawa, H.,Otaki, S.,Satoh, M.,Shitara, K.,Kato, K.
Structural comparison of fucosylated and nonfucosylated fc fragments of human immunoglobulin g1
J.Mol.Biol., 368:767-779, 2007

PubMed Abstract: 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.

PubMed: 17368483
DOI: 10.1016/j.jmb.2007.02.034

Experimental method

X-RAY DIFFRACTION (2.2 Å)