Asn297

Asn297 refers to the asparagine residue at position 297 in the heavy chain of immunoglobulin G (IgG). It is the canonical N-linked glycosylation site in the Fc region, located within the CH2 domain. The typical N-glycosylation motif, Asn-X-Ser/Thr, is present at this position in most IgG subclasses, where X is any amino acid except proline.

Glycosylation at Asn297 is added co-translationally in the endoplasmic reticulum and further processed in the Golgi apparatus. The attached glycan is usually a complex biantennary structure, often with core fucosylation, and contributes to Fc domain stability and conformation. The presence and composition of the glycan at Asn297 influence the Fc region’s interactions with Fc gamma receptors (FcγRs) and with the complement component C1q, thereby modulating effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Alterations at this site, including removal of the glycan (aglycosylation) or changes in glycan composition (notably fucosylation status), can significantly affect receptor binding and immune activity. In therapeutic antibodies, engineering the glycan at Asn297 is a common strategy to adjust efficacy and safety; for example, afucosylated antibodies often exhibit enhanced ADCC due to higher affinity for FcγRIIIa.

Asn297 is highly conserved in vertebrate IgG and serves as a key determinant of Fc behavior. Analytic approaches to study it include site-specific glycan analysis and mass spectrometry.