BIOCHEMISTRY - L. Stryer - 1984

VOLUME 1

PART I. CONFORMATION AND DYNAMICS

CHAPTER 9. CONNECTIVE TISSUE PROTEINS: COLLAGEN, ELASTIN, AND PROTEOGLYCANS

Summary

Collagen is a family of closely related Proteins with high tensile strength. It is the primary fibrous component of Skin, bone, tendon, Cartilage, Blood Vessels, and Teeth. Four types of collagen are known, differing in their tissue distribution. The basic structural unit of collagen is tropocollagen, which consists of three chains, each containing about 1000 amino acid residues. Collagen is remarkably rich in Glycine and Proline. In addition, it contains hydroxyproline and hydroxylysine, which are rarely found in other proteins. The Amino Acid Sequence of collagen is characterized by the fact that nearly every third residue is glycine. Tropocollagen is a triple-stranded helical rod 3000 A long and 15 A in diameter. The helical Structure of each individual tropocollagen chain is distinct from the α-Helix. Hydrogen Bonds form between the NH groups of glycine in one chain and the CO groups in the other two chains. Furthermore, the Stability of the Collagen helix depends on the steric constraint imposed by proline and hydroxyproline residues, as well as on hydrogen bonds formed by the hydroxyl groups of hydroxyproline. The interior of the triple helix is extremely crowded, which explains why glycine, being the smallest amino acid, must occupy every third position in The amino acid sequence of tropocollagen.

Proteolytic activation plays an important role in collagen Biosynthesis. The three chains of type I tropocollagen are synthesized as larger precursor molecules, pro-α1(I) and pro-α2. In these procollagen chains, certain proline residues are converted to hydroxyproline by prolyl hydroxylase. This enzyme requires O₂, Fe²⁺, and α-ketoglutarate for activity; ascorbic acid is also required as a reducing agent. Collagen synthesized in the absence of ascorbic acid is underhydroxylated and structurally weak, a condition characteristic of scurvy. Lysine is hydroxylated by another specific enzyme. Sugars are then attached to the hydroxylysine residues of the precursor chains. These hydroxylation and glycosylation processes occur within fibroblasts, after which the procollagens are secreted into the extracellular

space. Here, the amino- and carboxyl-terminal domains of the procollagen chains are cleaved by procollagen peptidases to yield tropocollagen, which spontaneously assembles into fibrils. The structural framework of collagen fibers consists of parallel arrays of tropocollagen molecules, staggered relative to one another by 1/4 of their length. The final step in the maturation of a collagen fiber is The formation of cross-links that provide additional strength. An example is the aldol cross-links formed by the Condensation of aldehydes produced by The oxidation of the side chains of certain lysine residues.

Elastin is an insoluble, rubber-like protein found in the elastic fibers of Connective Tissue. It can be reversibly stretched to several times its original length. Connective Tissues such as ligaments and the aortic arch are particularly rich in elastin. Like collagen, elastin is rich in proline and glycine; unlike collagen, it contains no hydroxylysine and very little hydroxyproline. The Amino Acid Composition of elastin is characterized by a marked predominance of nonpolar Amino Acids. The amino acid sequence of elastin exhibits a distinct periodicity. For instance, the sequence Pro-Gly-Val-Gly-Val is frequently repeated. Elastin is synthesized as a soluble precursor, which is subsequently converted into an insoluble form through the formation of various cross-links. One such cross-link is desmosine, a derivative of four lysine residues. As in collagen, the formation of cross-links in elastin involves aldehydes as intermediates.

The second major macromolecular component of connective tissue, Proteoglycans, consists of polysaccharide and protein components. The polysaccharide chains, called glycosaminoglycans, are built of repeating disaccharide units that carry a high negative charge. Proteoglycans constitute the ground substance of connective tissue and determine its viscoelastic properties.