Glycoprotein

Glycoproteins are macromolecules, which consist of a protein and one or more covalently attached carbohydrate moieties (sugar groups). The carbohydrate groups are generally attached as a posttranslational modification to asparagine, serine, threonine or hydroxylysine residues covalently. This process is called glycosylation ( addition of sugars ). The bound carbohydrate residues vary greatly in size, ranging from monosaccharides via di-and oligosaccharides to polysaccharides. The carbohydrate portion of glycoproteins in may be from a few percent ( ribonucleases, thyroglobulin ) to 85% ( blood group antigens).

In the organism glycoproteins can fulfill numerous functions. They serve as structural elements ( structural proteins) of the cell membranes, as a lubricant (for example, as a component of mucus) and cell interaction (membrane proteins). Also, include some hormones (eg, thyroid stimulating hormone, hCG ) and components of the immune system (immunoglobulins, interferons ) to the glycoproteins.

Glycoproteins are widespread in nature and it is believed that there is probably more proteins covalently bonded carbohydrates as carbohydrate-free proteins. Sugar residues can assist in protein folding and increase the stability of proteins. Often proteins that perceive in the extracellular space project ( transmembrane proteins) or extracellular functions, carbohydrate residues wear. All export proteins and membrane proteins are or were during their biosynthesis glycoproteins. Glycoproteins therefore also play an important role in recognition reactions by the immune system, especially in mammals. Examples include antibodies and the proteins of the MHC, which interact with T- cells or T-cell receptors.

Solutions of glycoproteins are often very viscous. In human blood plasma many plasma proteins have been isolated, of which only albumin and prealbumin have no sugar residues.

Occurring carbohydrates

In human glycoproteins only eight sugars play an important role. These are

• L- fucose ( Fuc ),
• D- galactose (Gal),
• D-mannose (Man),
• D-glucose (Glc ),
• D -xylose ( Xyl ),
• D-N- acetylglucosamine ( GlcNAc),
• D-N- acetylgalactosamine ( GalNAc ),
• DN- acetylneuraminic acid ( Neu5Ac ) is mainly found at the end of the oligosaccharide chains, usually linked to galactose or N- acetylgalactosamine.

During the synthesis of glycoproteins, the sugar are usually derived from nucleotides.

Glycoproteins often contain sulfates, which are normally bound to galactose, N- acetylgalactosamine or N- acetylglucosamine.

Binding

The binding of the oligosaccharides to the protein can be carried out in various ways.

N- glycosidic bond

Here, the bonding of the sugar is carried out on the nitrogen of the free amide group of asparagine (N in the one-letter code of amino acids ). N-glycosylation is carried out in the endoplasmic reticulum (ER). N- glycosides are the most important group of glycoproteins represents, and a variety of plasma proteins, but also membrane-bound proteins are among them.

Typical of the N- glycosylation is the synthesis of a independently formed from the amino acid sequence of the target protein to the sugar precursor dolichol carrier molecule, is present in the membrane of the ER. Dolichol is an isoprenoid 10-20 isoprene units, which carries an-OH group at the end, which is in turn linked to a diphosphate. The oligosaccharide precursor is formed at the terminal phosphate residue and consists of 14 hexoses, whose sequence is conserved evolutionarily among all eukaryotes. The first seven sugars are assembled in cytosolic side: the first two N-acetyl- glucosamine are added to the dolichol phosphate, then five mannose residues. As donors, the sugar - nucleotides UDP-N -acetyl- glucosamine and GDP-mannose were identified. The precursor of seven sugars is brought by a transport protein from the group of Phospholipidtranslokatoren ( Flippasen ) across the ER membrane, so it will be oriented toward the ER inside. Four mannose residues are added to the structure, followed by three glucose residues. The monosaccharides for this last step also come from a dolichol phosphate. The precursor of 14 sugars can then be transferred to a suitable protein. The minimum Glykolysierungssequenz is -Asn-X-Ser/Thr- (X = any amino acid except proline).

N- glycosidically linked glycoproteins are divided according to the proportion of monosaccharides contained in three groups: mannosereicher type ( high- mannose ), Complex ( Complex) and hybrid. The high-mannose type is characterized by a predominant proportion of mannose residues, saccharides complex type can contain any other saccharide mannose addition. Hybrid refers to a mixture of both types.

O- glycosidic bond

Here, the bonding of the sugar is carried out on the hydroxy group of serine, threonine, hydroxyproline or hydroxylysine. The O-glycosylation occurs in the Golgi apparatus.

Membrane proteins

The sugar residues of membrane proteins are oriented exclusively to the extracellular side of the membrane and form the glycocalyx. The degree of glycosylation of membrane proteins varies from cell type to cell type; per glycoprotein can occur up to a few hundred sugar residues.

Animal membranes with an average of three percent ( w / w) relatively little glycosylated. However plant membranes up to twenty percent (w / w) sugar residues which are mainly linked to membrane proteins (the rest of the lipids ).