Biochemistry: The Chemical Reactions of Living Cells, Volume 1 - D. Metzler 1980

The Molecules of Which We Are Made
Proteins
Sizes and Shapes of Protein Molecules

Both the Internal Structure of Proteins and their size and shape can vary widely. Fig. 2-12 provides some insight into the structural possibilities, illustrating several ways to fold a polypeptide chain consisting of 300 amino acid residues. In a fully extended conformation, the chain stretches to ~ 100 nm. If folded 13 times, the resulting pleated sheet forms a square with 7 nm sides and a thickness of about 0.5 nm. Alternatively, the same polypeptide chain can form a thin alpha-helical rod 45 nm long and ~ 1.1 nm thick. Combined with two other identical chains (given the appropriate Amino Acid Composition), this chain can yield a Collagen-like triple helix 87 nm long and ~ 1.5 nm in diameter. (Note that this corresponds to about 1/3 of the length of a tropocollagen molecule.)

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FIG. 2-12. Shapes that can be assumed by a protein molecule consisting of 300 amino acid residues (molecular weight —34,500).

Globular proteins vary markedly in packing density and Hydration Water content [24, 25]. However, a density of ~ 1.4 g∙cm^-3 is most typical for them. With an average residue mass of 115 daltons, our 300-residue polypeptide will have a mass of 34,500 daltons, or 5.74∙10^-20 g, and occupy a volume of 41 nm³. This could be a cube with an edge of 3.45 nm, a parallelepiped with dimensions of 1.8X3.6x6.3 nm, a sphere with a diameter of 4.3 nm, or some highly irregular geometric body. In calculations, protein molecules are most often represented as idealized ellipsoids or cylinders.

It is instructive to compare these dimensions with those of the smallest cellular structures; for instance, a bacterial flagellum has a diameter of ~ 13 nm, while a Cell membrane is ~ 8–10 nm thick. Building blocks equivalent in size to a 300-residue chain can form bacterial flagella or eukaryotic microtubules. An alpha-helical polypeptide can span The Cell membrane, protruding on both sides, whereas a globular protein with the same chain length will fit entirely within the membrane.

Box 2-A

Plasma Proteins

Of all proteins, those present in Blood Plasma are the most thoroughly studied^b,c. Their ease of isolation and great clinical significance led to these proteins being separated electrophoretically even in the Cytology/cytology/16.html">Early stages of research. Electrophoresis at pH 8.6 (in barbital buffer) reveals the presence of six major components. Serum albumin, which is present in the highest amounts, migrates the fastest. It is followed by a₁-, a₂-, and ß-globulins, fibrinogen, and y-globulins. Starch gel electrophoresis splits each of these bands, ultimately yielding about 20 bands. As a rule, each band contains more than one protein. In total, over 50 plasma proteins have been isolated and well characterized. Approximately 60 Enzymes have been detected in plasma, some present in very low amounts—evidently reflecting the leakage of small quantities of intracellular proteins into the plasma.

Under normal conditions, the total serum protein content ranges from 5.7 to 8.0 g per 100 ml (~ 1 mM). The concentration of individual proteins varies from 3.5–4.5 g per 100 ml for albumin down to a few milligrams or less for certain other proteins. IMMUNOGLOBULINS are the second most abundant group (Box 5-E); the concentration of one of them (IgG) reaches 1.2–1.8 g per 100 ml. a₁-Antitrypsin, a₂-macroglobulin, a- and ß-Lipoproteins, haptoglobin, transferrin, and fibrinogen are present in amounts exceeding 200 mg per 100 ml.

Plasma Proteins perform a multitude of Functions. One of these, characteristic primarily of serum albumin, is to maintain a sufficiently high osmotic pressure in plasma, comparable to that in the Cytoplasm of Cells. Human serum albumin consists of a single chain containing 584 amino acid residues, with a Molecular Weight of 69,000. Its molecule contains three repeating homologous regions—three domains, each of which contains six disulfide bridges. It can be postulated that during evolution, the Gene determining this protein underwent two duplications^г. The relatively low molecular weight and high density of negative charges on the molecular surface greatly assist serum albumin in carrying out its function of maintaining osmotic pressure.

Another vital function of Serum proteins is transport. For instance, serum albumin binds and transports many sparingly soluble metabolic products. Transferrin transports iron, and ceruloplasmin (an a₂-protein, see Supplement 10-3) transports copper. Transcortin is a carrier for Steroid Hormones, particularly cortisol; retinol-binding protein serves as the carrier for vitamin A, and cobalamin-binding proteins transport vitamin B₁₂. Lipoproteins, which are subdivided into three main classes, transport Phospholipids, neutral Lipids, and cholesteryl esters^д. Lipid serves as the major component of these substances. The serum a₁ fraction contains high-density lipoprotein^е. The fraction migrating immediately ahead of the ß-proteins contains very-low-density lipoprotein, and low-density lipoprotein is present in the ß-fraction. All of these proteins are currently under intensive investigation. Much of the interest in them stems from their association with Vascular Diseases, as well as with the deposition of Cholesterol and other lipids carried by plasma proteins into atherosclerotic plaques.

Immunoglobulins, a₁-Trypsin inhibitor (Supplement 7-B), a dozen or more blood-clotting factors (Fig. 6-16), and Complement system proteins (Supplement 5-G) perform protective functions; this topic will be discussed in more detail later. Hormones, many of which are proteins (Table 16-1), are present in the blood while being transported to target Organs. The functions of A number of serum proteins remain unknown. These include, in particular, many Glycoproteins. The concentration of some of them, such as haptoglobin (as well as a₂-macroglobulin), tends to increase in A wide variety of pathological conditions.

^а Putnam F. W. ed., The plasma Proteins, 2nd ed., Vols. 1 and 2, Academic Press, New York, 1975.

⁶ White A., Handler P., Smith E. L., Principles of Biochemistry, 5th ed., Chapter 30, McGraw-Hill, New York, 1973.

^B Turner M. W., Hulme B., The Plasma Proteins: An Introduction, Pitman, London, 1971.

^r Behrens P. Q., Spiekerman A. M., Brown I. R., Fed. Proc., 34, 591 (1975).

^д Morrisett J. D., Jackson R. L., Gotto A. M., Jr., Annu. Rev. Biochem., 44, 183—207 (1975).

^e Schonfeld G., Pfleger B., Roy R., JBC 250, 7943—7950 (1975).