Journal
GENES TO CELLS
Volume 16, Issue 11, Pages 1071-1080Publisher
WILEY
DOI: 10.1111/j.1365-2443.2011.01552.x
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- National Institute of Biomedical Innovation (NIBIO)
- Academia Sinica
- National Synchrotron Radiation Research Center (Taiwan, ROC)
- Grants-in-Aid for Scientific Research [20107004] Funding Source: KAKEN
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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 Fc gamma receptor IIIa (Fc gamma RIIIa). Here, we present the 2.2-angstrom structure of the complex formed between nonfucosylated IgG1-Fc and a soluble form of Fc gamma RIIIa (sFc gamma RIIIa) with two N-glycosylation sites. The crystal structure shows that one of the two N-glycans of sFc gamma RIIIa 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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