PMID: 22023369

 

    Legend: Sugar

Title : Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans.

Abstract :
  1. 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 )
  2. Here, we present the 2.2-Å structure of the complex formed between nonfucosylated IgG1-Fc and a soluble form of FcγRIIIa (s FcγRIIIa ) with two N-glycosylation sites
  3. The crystal structure shows that one of the two N-glycans of s FcγRIIIa mediates the interaction with nonfucosylated Fc, thereby stabilizing the complex
  4. 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
  5. Our results offer a structural basis for improvement in ADCC of therapeutic antibodies by defucosylation