Effects of O-Glycosylation on Protein Structure: The Role and Characterization of Heavily O-Glycosylated Mucin Domains

In another class of cell-surface glycoproteins (e.g., the low density lipoprotein receptor, thrombomodulin, decay accelerating factor, platelet glycoprotein lb, lactase-phlorizin hydrolase, and sucrase-isomaltose com­ plex [25-30]) mucin-like domains serve as proteolysis-resistant stalks tether­ ing functional globular domains (receptors or enzymes) to the cell surface. These stalks range from -2 0 to more than 100 residues and are found in proteins of varied biological functions, from the transport of cholesterol to modulating immune and coagulation responses. Heavily O-glycosylated domains are also found in a small number of nonmucin secreted proteins such as human serum immunoglobulin Al and D (IgAl, IgD) and k-casein [31-33], again acting presumably to provide extended structural motifs that may be important for function. Heavily O-glycosylated glycoprotein domains are also common in lower organisms including fungi and slime molds [34,35].