The number of N-glycans (n) is a distinct feature of each glycoprotein sequence and cooperates with the physical properties of the Golgi N-glycan-branching pathway to regulate surface glycoprotein levels. The Golgi pathway is ultrasensitive to hexosamine flux for the production of tri- and tetra-antennary N-glycans, which bind to galectins and form a molecular lattice that opposes glycoprotein endocytosis. Glycoproteins with few N-glycans (e.g., TbetaR, CTLA-4, and GLUT4) exhibit enhanced cell-surface expression with switch-like responses to increasing hexosamine concentration, whereas glycoproteins with high numbers of N-glycans (e.g., EGFR, IGFR, FGFR, and PDGFR) exhibit hyperbolic responses. Computational and experimental data reveal that these features allow nutrient flux stimulated by growth-promoting high-n receptors to drive arrest/differentiation programs by increasing surface levels of low-n glycoproteins. We have identified a mechanism for metabolic regulation of cellular transition between growth and arrest in mammals arising from apparent coevolution of N-glycan number and branching.

It is well established that high doses of monomeric immunoglobulin G (IgG) purified from pooled human plasma [intravenous immunoglobulin (IVIG)] confer anti-inflammatory activity in a variety of autoimmune settings. However, exactly how those effects are mediated is not clear because of the heterogeneity of IVIG. Recent studies have demonstrated that the anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Here we determine the precise glycan requirements for this anti-inflammatory activity, allowing us to engineer an appropriate IgG1 Fc fragment, and thus generate a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. This therapeutic molecule precisely defines the biologically active component of IVIG and helps guide development of an IVIG replacement with improved activity and availability.

In Rhizobium leguminosarum biovar viciae, the nodABC and nodFEL operons are involved in the production of lipo-oligosaccharide signals which mediate host specificity. The structure of these metabolites and those produced in nod mutants links the nodE and nodL genes to specific chemical features of the signal molecules. A nodE-determined, highly unsaturated fatty acid and a nodL-determined O-acetyl substituent are essential for the ability of the signals to induce nodule meristems on the host plant Vicia sativa.