- Related Topics:
- enzyme
- transcription factor
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- prion
- protein phosphorylation
- Notable Honorees:
- Rodney Robert Porter
Despite its weaknesses, a functional classification is used here in order to demonstrate, whenever possible, the correlation between the structure and function of a protein. The structural, fibrous proteins are presented first, because their structure is simpler than that of the globular proteins and more clearly related to their function, which is the maintenance of either a rigid or a flexible structure.
Structural proteins
Scleroproteins
Collagen
Collagen is the structural protein of bones, tendons, ligaments, and skin. For many years collagen was considered to be insoluble in water. Part of the collagen of calf skin, however, can be extracted with citrate buffer at pH 3.7. A precursor of collagen called procollagen is converted in the body into collagen. Procollagen has a molecular weight of 120,000. Cleavage of one or a few peptide bonds of procollagen yields collagen, which has three subunits, each with a molecular weight of 95,000; therefore, the molecular weight of collagen is 285,000 (3 × 95,000). The three subunits are wound as spirals around an elongated straight axis. The length of each subunit is 2,900 angstroms, and its diameter is approximately 15 angstroms. The three chains are staggered, so that the trimer has no definite terminal limits.
Collagen differs from all other proteins in its high content of proline and hydroxyproline. Hydroxyproline does not occur in significant amounts in any other protein except elastin. Most of the proline in collagen is present in the sequence glycine–proline-X, in which X is frequently alanine or hydroxyproline. Collagen does not contain cystine or tryptophan and therefore cannot substitute for other proteins in the diet. The presence of proline causes kinks in the peptide chain and thus reduces the length of the amino acid unit from 3.7 angstroms in the extended chain of the β-structure to 2.86 angstroms in the collagen chain. In the intertwined triple helix, the glycines are inside, close to the axis; the prolines are outside.
Native collagen resists the action of trypsin but is hydrolyzed by the bacterial enzyme collagenase. When collagen is boiled with water, the triple helix is destroyed, and the subunits are partially hydrolyzed; the product is gelatin. The unfolded peptide chains of gelatin trap large amounts of water, resulting in a hydrated molecule.
When collagen is treated with tannic acid or with chromium salts, cross links form between the collagen fibers, and it becomes insoluble; the conversion of hide into leather is based on this tanning process. The tanned material is insoluble in hot water and cannot be converted to gelatin. On exposure to water at 62° to 63° C (144° to 145° F), however, the cross links formed by the tanning agents collapse, and the leather contracts irreversibly to about one-third its original volume.
Collagen seems to undergo an aging process in living organisms that may be caused by the formation of cross links between collagen fibers. They are formed by the conversion of some lysine side chains to aldehydes (compounds with the general structure RCHO), and the combination of the aldehydes with the ε-amino groups of intact lysine side chains. The protein elastin, which occurs in the elastic fibers of connective tissue, contains similar cross links and may result from the combination of collagen fibers with other proteins. When cross-linked collagen or elastin is degraded, products of the cross-linked lysine fragments, called desmosins and isodesmosins, are formed.
Keratin
Keratin, the structural protein of epithelial cells in the outermost layers of the skin, has been isolated from hair, nails, hoofs, and feathers. Keratin is completely insoluble in cold or hot water; it is not attacked by proteolytic enzymes (i.e., enzymes that break apart, or lyse, protein molecules), and therefore cannot replace proteins in the diet. The great stability of keratin results from the numerous disulfide bonds of cystine. The amino acid composition of keratin differs from that of collagen. Cystine may account for 24 percent of the total amino acids. The peptide chains of keratin are arranged in approximately equal amounts of antiparallel and parallel pleated sheets, in which the peptide chains are linked to each other by hydrogen bonds between the carbonyl and imino groups.
Reduction of the disulfide bonds to sulfhydryl groups results in dissociation of the peptide chains, the molecular weight of which is 25,000 to 28,000 each. The formation of permanent waves in the beauty treatment of hair is based on partial reduction of the disulfide bonds of hair keratin by thioglycol, or some other mild reducing agent, and subsequent oxidation of the sulfhydryl groups (―SH) in the reoriented hair to disulfide bonds (―S―S―) by exposure to the oxygen of the air.
The length of keratin fibers depends on their water content. They can bind approximately 16 percent of water; this hydration is accompanied by an increase in the length of the fibers of 10 to 12 percent.
The most thoroughly investigated keratin is hair keratin, particularly that of wool. It consists of a mixture of peptides with high and low cystine content. When wool is heated in water to about 90° C (190° F), it shrinks irreversibly. This is attributed to the breakage of hydrogen bonds and other noncovalent bonds; disulfide bonds do not seem to be affected.
Others
The most thoroughly investigated scleroprotein has been fibroin, the insoluble material of silk. The raw silk comprising the cocoon of the silkworm consists of two proteins. One, sericin, is soluble in hot water; the other, fibroin, is not. The amino acid composition of the latter differs from that of all other proteins. It contains large amounts of glycine, alanine, tyrosine, and serine; small amounts of the other amino acids; and no sulfur-containing ones. The peptide chains are arranged in antiparallel β-structures. Fibroin is partly soluble in concentrated solutions of lithium thiocyanate or in mixtures of cupric salts and ethylene diamine. Such solutions contain a protein of molecular weight 170,000, which is a dimer of two subunits.
Little is known about either the scleroproteins of the marine sponges or the insoluble proteins of the cellular membranes of animal cells. Some of the membranes are soluble in detergents; others, however, are detergent-insoluble.
