Collagens.
The family of collagens includes about 20 proteins. Collagen is produced mainly by fibroblasts. It is about 30% of the total amount of protein of an adult, or 6% of body weight. A characteristic component of connective tissue structure is collagen fibers. They consist of elongated protein molecules of tropocollagen. This is the basic structural unit of collagen.
Fibril-forming collagens
Molecules of collagens I, II, III, V, XI are formed by three polypeptide chains, each of which is curled in left-handed helix, as they are twisted together in the right-hand super helix. Collagen is characterized by specific amino acid composition. 1/3 of all amino acid residues is glycine, 1/3 is proline and 4-hydroxyproline, about 1% is hydroxylysine; some forms of collagen contain 3-hydroxyproline.
Structural residue Gly-X-Y, often repeated in the primary structure of polypeptide chains of collagen, is called the collagen motive. Glycine is required, because any other amino acid radical cannot fit between the polypeptide chains in the center of the triple helix. X is often proline (or lysine), and Y is hydroxyproline (or another amino acid). They limit the rotation of the polypeptide chain. Triple helix is stabilized by hydrogen bonds with residues of hydroxyproline and water molecules (interfibrillar structural water) and interchain cross-links between lysine and hydroxylysine residues.
Collagen, forming a tela
Type IV collagen is the main structural protein of basement membranes. Its peptide chains remain globular end domains and form a reticular three-dimensional structure.
Collagen synthesis occurs on polyribosomes of ER. With the participation of prolylhydroxylase or lysylhydroxylase enzymes proline and lysine residues in the growing chains are hydroxylated with the participation of oxygen, -ketoglutarate and Fe2 + ion and ascorbic acid as cofactors. Hydroxylation is necessary for the formation of bonds between the molecules of collagen fibrils assembly.
During the synthesis peptide chains with the help of signal peptide penetrate through the membrane into the cavity of the ER, there they are glycosylated by attaching monosaccharide residues to certain residues of hydroxylysine and then combine to form molecules of procollagen. It moved to the Golgi complex, is included in the secretory granules and is secreted. In the intercellular space terminal propeptides are cleaved from procollagen by the influence of amino- and carboxypeptidases, and tropocollagen is formed.
Collagen fibrils formation occurs by self-assembly. There is a deamination of lysine and hydroxylysine to form an aldehyde group. They interact with the amino group of lysine residue of another molecule of collagen. Intermolecular covalent cross-linkers are formed.
2. Elastin is the main protein component, from which the elastic fibers consist of. Like collagen, elastin contains a lot of glycine and proline. Elastin contains oxyproline in about 10 times less than collagen; there is no hydroxylysine, a lot of valine and other hydrophobic amino acids.
Elastin peptide chain is in the form of loose globule. In the intercellular matrix elastin molecules are linked by crosslinks, in the formation of which lysine residues are involved. As a result elastinic fibers and layers are formed. Elastin, unlike other fibrous proteins can be stretched in two directions.
Elastin is synthesized by fibroblasts. Its predecessor is tropoelastin. It does not contain cross-linking bonds, and it is soluble. Then tropoelastin turns into a mature insoluble elastin, which contains a large number of cross-links. It is contained in large blood vessels, ligaments, lungs.
3. Non-collagenic structural glycoproteins.
Fibronectin is a dimer. Its subunits are joined anti-parallel by two disulfide bonds in the area of C-terminal ends. The peptide chain forms several globular domains. The molecules have an elongated shape and have binding sites with other molecules of fibronectin, with collagen, glycosaminoglycans, integrins.
Laminin is heterotrimer. Laminin molecule has a cruciform shape, with three short branches, each of which contains globular domains, and a long branch with a C-terminal globular domain. Laminin in basal membranes is in a complex with another protein – nidogene. Nidogen has binding sites of collagen. It provides the integration main components of the basement membrane. In the presence of Ca2 + laminin by self-assembly forms tela due to the interaction of the globular domain of short branches.
4. Proteoglycans are high-molecular carbohydrate-protein compounds. They are up to 30% of the dry mass of connective tissue.
Polysaccharide group of proteoglycans called mucopolysaccharides (these substances are found mainly in the mucous substrates). Later they became known as glycosaminoglycans. These are linear unbranched polymers built of repeating disaccharide units. They are composed of glucosamine or galactosamine residues, as well as D-glucuronic or L-iduronic acid residues.
First hyaluronic acid was detected in the vitreous body.
It is built from the residues of glucuronic acid and N-acetylglucosamine. It is contained in the heart valves, cartilage. Its main function is the binding of water. It is involved in regulation of tissue permeability.
Chondroitin sulphates containe glucuronic acid and sulphuretted N-acetylgalactosamine. Chondroitin-6-sulphate is contained in the heart valves, and chondroitin-4-sulfate is contained in the cartilage.
Dermatan sulphate is found in the dermis (skin). L-iduronic acid is in the composition of dermatan sulphate. It is involved in the stabilization of collagen bundles.
Keratan sulphate was first isolated from bovine cornea. It does not contain D-glucuronic or L-iduronic acids. Keratan sulphates from different tissues have varying degrees of sulphonation and the type of connection to the protein.
Heparin is synthesized by mast cells. It exists in the form of single polysaccharide chains, or in the form of proteoglycans. Heparin is anticoagulant, it is involved in the regulation of blood clotting.
The biosynthesis of glycosaminoglycans.
Glucosamine and glucuronic acid are synthesized from D-glucose. Further there is epimerization of glucosamine into galactosamine, and glucuronic acid – into iduronic acid. Predecessors of hyaluronic acid are uridinediphosphonucleotide derivatives of N-acetylglucosamine and glucuronic acid.
The protein part of proteoglycans is synthesized on polyribosomes of ER. Synthesis of carbohydrate part begins in the cavity of the ER. Here is its sulphonation. Simultaneously with the synthesis of polysaccharide chains proteoglycan molecule moves in the direction of lamellar complex, where it is included in the secretory granules and subjected exocytosis.
Different proteoglycans have different protein components; they have nothing in common with collagen and elastin. A large number of glycosaminoglycan chains are connected through the hydroxyl group of serine with one peptide chain, so that the molecule resembles a brush. In the intercellular substance proteoglycans are contained mainly in the complexes with hyaluronic acid.
Proteoglycan molecules are "fluff" in a solution because of the repulsion of negatively charged sulphonated glycosaminoglycan chains and also due to hydration. It is important for cartilage of joint surfaces, where proteoglycans act as springs.
Integration of the extracellular matrix and cells is provided by adhesion molecules.
Integrins are transmembrane proteins; they are dimers. They provide a transmembrane signal transduction. Both integrin chains have large extracellular and short intracellular domains. When in the matrix changes occur in the extracellular domain of the integrin, the signal is transmitted to the intracellular domain and regulatory cytoplasmic proteins are associated with it. Signaling by integrins from outside to inside leads to a change in the synthesis and secretion of extracellular matrix components or synthesis and secretion of enzymes that destroy the components of the matrix. Similarly, the signal transmission occurs from the inside out.