alpha16fucosyltransferases

Alpha-1,6 fucosylation, or core fucosylation, is the enzymatic addition of a fucose residue in an alpha-1,6 linkage to the innermost N-acetylglucosamine of N-linked glycans on glycoproteins. It occurs in the Golgi and uses GDP-fucose as the donor substrate.

In mammals, the core fucosyltransferase FUT8 is the primary enzyme responsible for this modification. FUT8 uniquely transfers fucose to the innermost GlcNAc, whereas other fucosyltransferases create fucose linkages at outer positions (antennae).

Core fucosylation modulates protein function by affecting receptor signaling and ligand binding. It influences the activity of growth factor receptors such as TGF-β and EGFR, and it shapes antibody interactions with Fc receptors. Specifically, antibodies lacking core fucose show higher affinity for FcγRIIIa and enhanced antibody-dependent cellular cytotoxicity.

Genetic disruption of FUT8 or core fucosylation results in developmental abnormalities in model organisms; in humans, altered core fucosylation has been linked to immune dysfunction and cancer progression, making it a focus of biomedical research and therapeutic antibody engineering.

Analytical approaches include mass spectrometry-based glycomics and lectin assays; genetic models help define FUT8 function. In biopharmaceuticals, engineering afucosylated antibodies is a strategy to boost effector function, illustrating the practical relevance of core fucosylation in medicine.