Title : Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans
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 (s FcγRIIIa ) with two N-glycosylation sites
- The crystal structure shows that one of the two N-glycans of s FcγRIIIa 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
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. defucosylation, , -, their Fc glycans, -
- 2. N-glycosylation, , -, -, sites
- 2. nonfucosylated, , IgG1, -, -
- 3. sFcγRIIIa, , FcγRIIIa, the two N-glycans, -
- 4. fucosylation, , -, the Fc N-glycans, site
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):