Quick glance about Glycoproteins

Glycoproteins:
Glycoproteins, a wide range of compounds with a variety of structure and function, are parts of cell membranes, intercellular matrices, and extracellular fluids, such as plasma. The percentage of carbohydrate varies considerably in glycoproteins derived from different tissues or from different sources. For example, collagen contains an amount of carbohydrate that differs with the source: skin tissue collagen, about 0.5%; cartilage collagen, about 4%; and basement membrane collagen, more than 10%. Glycoproteins containing high percentage of carbohydrate include glycophorin, a membrane component of human erythrocytes, about 60%, and soluble blood group substances, as much as 85%. In glycoproteins, the protein and the carbohydrate molecules are bound in covalent linkage. There are five common kinds of carbohydrate, four of which are common to human glycoproteins.

Glycoproteins and their Functions:

Glycoproteins	Function
Collagen	Structure
Epithelial mucins, Synovial fluid glycoproteins	Lubrication and protection
Ceruloplasmin, Transferrin	Transport
Thyrotropin, Chorionic gonadotropin, Erythropoietin	Endocrine regulation
Proteases, Nucleases, Glycosidases, Hydrolases	Catalysis
Immunoglobulins, Complement protein, Interferon	Defense against infection
Receptors for hormones, acetylcholine, cholera toxin, electromagnetic radiation	Membrane receptors
Blood group substances	Antigens
Fibronectin, laminin, chondronectin	Cell-cell recognition and adhesion
Glycophorin, intrinsic factor, clotting factors	Miscellaneous

Collagen:

Collagen is abundant protein in animal kingdom which is important component of connective tissues. Animals are able to stretch, bend and move because of collagen.

Mucins:

Mucins are glycoproteins which are secreted by salivary glands. Mucins are rich in proline, serine and threonine.

Ceruloplasmin:

It is copper carrying protein synthesized in liver. If copper is not attached to ceruloplasmin, the condition result in copper poisoning. This is called Wilson disease.

Transferrin:

It is iron transferring plasma protein to spleen, liver and bone marrow via blood. It plays important role in nutritional issues.

Fibronectin:

Fibronectin, a glycoprotein abundant on the cell surface of normal cells, promotes that attachment and subsequent spreading of many cell types. Known also as a cell surface protein, fibronectin is a large, external, transformation-sensitive protein that binds to a number of substances.

RBC membrane and membrane skeleton proteins:

A major integral membrane glycoprotein of human RBCs, glycophorin A, has been characterized. It has a molecular weight of 31,000. Each membrane comprises more than 400,000 molecules of glycophorin, accounting for more than 1.5 % of the weight of the membrane. The polypeptide comprises of 131 amino acid residues. Glycophorin A possess 16 oligosaccharide units, of which 15 are linked by O-glycosidic bonds to serine or threonine residues and one is linked by an N-glycosidic bond. The N-linked oligosaccharide possesses mannose. All of the oligosaccharide chains can be seen in the 50 residues of the amino terminal domain, in which amino acid molecules 2-4 and 10-15 all carry an oligosaccharide
unit in O-glycosidic linkage. The middle hydrophobic region is believed to possess an α-helical structure.
Glycophorin possesses antigenic determinants for blood groups M and N. The M and N antigenic determinants are present on glycophorin A and glycophorin B, respectively. The first one differs from
the second at positions 1 and 5 of the amino terminal end

NH2-Ser-Ser-Thr-Thr-Gly-

Glycophorin A

NH2-Leu-Ser-Thr-Thr-Glu-

Glycophorin B

Glycophorin A is present in type M, glycophorin B in type N, and both glycophorins in type MN individuals. Antibodies targetted against M and N do not cross-react and can distinguish sequence variations between the two glycophorins.

The RBC membrane skeleton comprises predominantly of four proteins: spectrin, actin, protein 4.1, and ankyrin (also known as syndein).

• Spectrin, an extrinsic protein present on the cytoplasmic surface of the membrane, was so called because of its extraction from RBC ghosts. It comprises morethan 25% by weight of the membrane proteins. 
• Spectrin is a long and unusually flexible molecule comprising of two structurally and functionally different polypeptide chains arranged side by side to form a heterodimer. It assumes a variety of conformations that may be important for flexibility and deformability. 
• The lateral connections of spectrin are formed by head-to-head association of heterodimers to form heterotetramers or perhaps higher order oligomers. 
• Spectrin can also attach at one end to short filaments of actin comprising of 10-20 monomers. The monomer is known as G-actin and the polymer as F-actin. Actin is present in all eukaryotic cells, and its role in muscle contraction is well established. 
• The spectrin-actin interaction is cooperatively strengthened by protein 4.1, a globular protein that binds to spectrin at the tail end of the molecule in close proximity to the actin binding site. 
• Spectrin is attached to the inner membrane surface by means of two proteins: ankyrin, or syndein,and anion exchange protein. 
• Spectrin is bound to ankyrin, a large protein of pyramidal shape, which ties the membrane skeleton through its connection to the anion exchange protein. 
• The latter is an integral membrane glycoprotein that spans the lipid bilayer and functions in exchange of CI- for HCO3. Protein 4.1 may also bind the actin-spectrin complex to the transmembrane glycoprotein glycophorin.

Blood Group Antigens:

• Antigenic determinants known as blood group substances are present on the surface of human red
• blood cells. The ABO blood group system is associated with three antigens: A, B, and H. 
• The specificity of these antigens resides in difference of the terminal carbohydrate residue. Addition of an N-acetylgalactosamine residue to an H antigen yields an A antigen, whereas addition of a galactose residue yields a B antigen. 
• The H antigen itself is synthesized by addition of a fucosyl residue to a precursor oligosaccharide. The classification of individuals into ABO types is based upon whether A or B antigens are present or not; type A individuals have the A antigen, type B, the B antigen, and type O, the H antigen, respectively. 
• Normally, an antigen and its specific antibody are not present simultaneously. For example, individuals having type A red blood cells possess anti-B antibodies; those of type B possess anti-A antibodies; those of type AB have neither of these antibodies; and those of type O have both anti-A and anti-B antibodies. 
• Rh blood group antigens are clinically important due to their involvement in hemolytic disease of the newborn, transfusion medicine, and autoimmune hemolytic anemia.
• The designation of Rh stands for Rhesus because the antibody specificity was identical to that of antibodies generated in rabbits injected with red blood cells from Rhesus monkeys. 
• The Rh blood group system consists of more than 50 nonglycosylated protein antigens; however, only five are commonly identified; these are encoded by two genes termed RHD and RHCED. Marked racial differences are observed for Rh alleles in different populations. Typically, 85% of all Caucasians are Rho(D)-positive.
• Anti-Rho(D) immunoglobulin G (IgG) prepared from human plasma is administered intramuscularly as means of passive immunization to Rho(D)-negative individuals exposed to Rho(D)-positive cells. Rh proteins have a molecular weight of about 32,000 and span the red blood cell membrane. 
• Rh proteins are incorporated into the erythrocyte membrane after palmitolyation via thioester linkages involving free sulfhydryl groups of cysteine residues. 
• The exact function of Rh proteins is not known, however, individuals lacking all Rh protein expression exhibit multiple red blood cell abnormalities including abnormal morphology and survival. This condition is known as Rhnull syndrome.

ABO blood group system

Blood type	Types of oligosaccharide anigens	Antibody in serum	Types of serum that cause agglutination
O	H	Anti-A, anti-B	None
A	A	Anti-B	O,B
B	B	Anti-A	O,A
AB	A and B	None	O,A,B

Functions of blood group protein Ag of RBC:

Blood group	Protein
Proteins that contribute to the structural Integrity: Rhesus(Rh) Gerbich (Ge) Diego (Di), Wright (Wr) XK	Rh acylproteins Glycophorins C  and D Anion channel protein Kx protein
Proteins with complement related functions: Cromer (Cr)	Decay accelerating factor (CD55)
Proteins with receptor functions: Duffy	Chemokine receptor
Protein with transport functions: Diego (Di), Wright (Wr) Kidd (Jk) Colton (Co)	Anion channel protein Urea transporter Aquaporin 1 water channel protein
Proteins with enzymatic activity: Kell (K,k,Kp,Js) Cartwright (Yt)	93kD protein, metalloproteinase Acetylcholinesterase

Blood group antigen-bearing proteins also serve as receptors for infection agents. A notable example is the presence of receptors in the Duffy blood group antigens to Plasmodium vivax and Plasmodium knowlesi. Individuals who do not express Duffy antigens are resistant to infection by these malarial parasites.