The Architecture of Folded Proteins

All proteins are made in the same way but as the growing peptide chains peel off from the ribosome, each of the thousands of different proteins in a living cell folds into its own special tertiary structure. The number of possible conformations of a protein chain is enormous. Consider a 300-residue polypeptide which could stretch in fully extended form for ∼100 nm. If the chain were folded back on itself about 13 times it could form a 7-nm square sheet about 0.5 nm thick. The same polypeptide could form a thin helical rod 45 nm long and ∼1.1 nm thick. If it had the right amino acid sequence it could be joined by two other similar chains to form a collagen-type triple helix of 87 nm length and about 1.5 nm diameter. The highly folded globular proteins vary considerably
in the tightness of packing and the amount of internal water of hydration. However, a density of ∼1.4 g cm–3 is typical. With an average mass per residue of 115 Da our 300-residue polypeptide would have a mass of 34.5 kDa or 5.74 x 10–20 g and a volume of 41 nm3. This might be approximated by a cube 3.45 nm in width, a “brick” of dimensions 1.8 x 3.6 x 6.3 nm, or a sphere of diameter 4.3 nm. Although protein molecules are usually very irregular in shape, for purposes of calculation idealized ellipsoid and rod shapes are often assumed.
It is informative to compare these dimensions with those of the smallest structures visible in cells; for example, a bacterial flagellum is ∼13 nm in diameter and a cell membrane ∼8–10 nm in thickness. Bricks of the size of the 300-residue polypeptide could be used to assemble a bacterial flagellum or a eukaryotic microtubule. Helical polypeptides may extend through cell membranes and project on both sides, while a globular protein of the same chain length may be almost completely embedded in the membrane.