3AY4

Crystal structure of nonfucosylated Fc complexed with bis-glycosylated soluble form of Fc gamma receptor IIIa

Summary for 3AY4

• Entry DOI: 10.2210/pdb3ay4/pdb
• Related: 1E4K 1T83 1T89 2DTS 3AVE
• Descriptor: Ig gamma-1 chain C region, Low affinity immunoglobulin gamma Fc region receptor III-A, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-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, ... (6 entities in total)
• Functional Keywords: immune system, complex, fc fragment, igg, receptor, cd16, gamma
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 75844.47

Authors

Mizushima, T.,Takemoto, E.,Yagi, H.,Shibata-Koyama, M.,Isoda, Y.,Iida, S.,Satoh, M.,Kato, K. (deposition date: 2011-04-28, release date: 2011-08-03, Last modification date: 2024-10-23)

Primary citation

Mizushima, T.,Yagi, H.,Takemoto, E.,Shibata-Koyama, M.,Isoda, Y.,Iida, S.,Masuda, K.,Satoh, M.,Kato, K.
Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans
Genes Cells, 16:1071-1080, 2011

PubMed 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.

PubMed: 22023369
DOI: 10.1111/j.1365-2443.2011.01552.x

Experimental method

X-RAY DIFFRACTION (2.2 Å)