Threonine glycoproteins

The TGF-P superfamily cell signaling pathways are well characterized (Figure 7.2). Cell signaling occurs through association with two transmembrane serine/threonine glycoprotein kinase receptors, type I... 

A variety of cellular and viral proteins contain fatty acids covalently bound via ester linkages to the side chains of cysteine and sometimes to serine or threonine residues within a polypeptide chain (Figure 9.18). This type of fatty acyl chain linkage has a broader fatty acid specificity than A myristoylation. Myristate, palmitate, stearate, and oleate can all be esterified in this way, with the Cjg and Cjg chain lengths being most commonly found. Proteins anchored to membranes via fatty acyl thioesters include G-protein-coupled receptors, the surface glycoproteins of several viruses, and the transferrin receptor protein. 

FIGURE 9.26 The carbohydrate tnoiedes of glycoproteins may be linked to the protein via (a) serine or threonine residues (in the O-linked saccharides) or (b) asparagine residues (in the N-linked saccharides), (c) N-Linked glycoproteins are of three types high mannose, complex, and hybrid, the latter of which combines structures found in the high mannose and complex saccharides. 

The major classes of glycoproteins are O-linked (involving an OH of serine or threonine), N-linked (involving the N of the amide group of asparagine), and glycosylphosphatidylinositol (GPi)-linked. 

Figure 52-6. Diagrammatic representation of the structures of the H, A,and B blood group substances. R represents a long complex oligosaccharide chain, joined either to ceramide where the substances are glycosphingolipids, or to the polypeptide backbone of a protein via a serine or threonine residue where the substances are glycoproteins. Note that the blood group substances are biantenna ry ie, they have two arms, formed at a branch point (not indicated) between the GIcNAc—R, and only one arm of the branch is shown. Thus, the H, A,and B substances each contain two of their respective short oligosaccharide chains shown above. The AB substance contains one type A chain and one type B chain.

Removal of the oligosaccharide chain from the glycoprotein usually involves the use of one of three main methods treatment with NaOH-NaBH4, hydrazinolysis, or proteolysis.34-36 The NaOH-NaBH4 treatment is used to release, somewhat specifically, oligosaccharides O-linked to serine and threonine. Hydrazinolysis is used to break N-linkages, and proteolysis, to isolate glycopeptides. Each method apparently still has some drawbacks. 

A number of the central themes of current glycoconjugate research can be traced back to studies begun in the Jeanloz laboratory. One prominent example is the elucidation of the sequences of the carbohydrates linked N- or O-glycosylically to asparagine or serine/threonine residues respectively in glycoproteins. Little was... 

Human IL-2 is a single-chain polypeptide containing 133 amino acids. It is a glycoprotein, the carbohydrate component being attached via an O-linked glycosidic bond to threonine... 

The oligosaccharide sequences just discussed are linked to glycoproteins through the following (generalized) N- and O-linked cores (to asparagine and serine or threonine, respectively). 

Glycoproteins are smaller than proteoglycans, and have far more variability in protein and carbohydrate content between different types. In both types of molecule, the oligosaccharide moieties are covalently attached to the protein via serine, threonine... 

An exotic function of glycoproteins is to act as antifreezes. Specifically, a number of Antarctic fish live in water cooled to about -1.9°C, a temperature below the freezing point of water and below that where the blood, mostly water, of these fish is expected to freeze. Clearly, this would be a disaster for these fish. They are saved from this fate by antifreeze glycoproteins. These proteins contain about 50 repeats of the tripeptide Ala-Ala-Thr. To each of these threonine residues is hooked a specific disaccharide. 

---