Glycoproteins - Hughes, R. 1985

Functions
Polypeptide processing

Many Polypeptides and Proteins are synthesized as giant precursors that are subsequently cleaved by specific proteases to yield "mature," biologically active products. Glycans likely play a crucial role in regulating such fragmentation. As bulky components of glycosylated polypeptides, they can modulate the Cleavage of specific chain segments, which is essential for generating active components. Below, we examine a relevant example.

The Pituitary Gland produces a wide array of biologically active Peptides, including adrenocorticotropin, melanotropin, and endorphins. Exactly how such a large variety of compounds arises became clear following the identification of a common precursor, the isolation of mRNA from the intermediate lobe of the pituitary gland, and the cloning of its genes. The availability of complementary DNA (cDNA) with a known Primary Structure made it possible to determine the arrangement of the regions encoding each active polypeptide. Flanking these regions are pairs of basic Amino Acids that can serve as recognition signals for highly specific pituitary peptidases with Trypsin-like activity. In the anterior lobe of the pituitary, fragmentation stops at the stage of an N-terminal fragment comprising N-glycans, corticotropin, and β-lipotropin. In the intermediate lobe, the latter two fragments are very rapidly cleaved into β-endorphin and α-melanotropin. Following Treatment with tunicamycin, an inhibitor of glycosylation, the Cells produce only very small amounts of biologically active peptides. This indicates that N-glycans somehow control the accessibility of sites destined for proteolysis. Only in fully glycosylated precursors are there basic amino acid-rich flanking regions susceptible to preferential cleavage by pituitary Enzymes, thereby triggering the cascade of reactions that yields biologically active fragments [54].