Configuration of certain protein molecules. An inquiry concerning the present status of our knowledge



It is now becoming possible to correlate studies on the general size and shape of protein molecules in solution with knowledge of the possible configurations of polypeptide chains and, in some instances, with that of the actual sequence of amino acid residues in these chains. The formation of helices and of “pleated sheets” from polypeptide chains, and the dimensions of these structures, are discussed, and the possible significance of proline residues for the bending and folding of chains is pointed out. The relation of purified protein preparations to the state of the proteins in their natural surroundings is discussed, as is the meaning of the concept of purity. Protein molecules are to be regarded as highly ordered and regular structures, but probably not as completely rigid. The meaning of the concept of protein hydration is considered, with reference to both external and internal hydration. The question of what can be learned from hydrodynamic measurements concerning the hydration and the shapes of protein molecules in solution is critically discussed.

The evidence available today concerning the size and shape of some particularly wellknown proteins is examined. These include beef insulin; horse heart myoglobin; horse hemoglobin; human and bovine serum albumin, including mercaptalbumin; human and bovine fibrinogen; rabbit myosin; and tobacco mosaic virus. The first three of these molecules are relatively small and symmetrical in shape. Serum albumin appears to be moderately asymmetrical, with an axial ratio of the order of 4 to 1. Fibrinogen, myosin and tobacco mosaic virus are highly asymmetrical. Although the chemical structure of insulin is now known in great detail, the shape of the molecule as a whole cannot yet be precisely specified. All the molecular models proposed for these proteins, except perhaps that for the virus, must be regarded as tentative and subject to revision.

Future prospects of progress in this area are considered, with particular emphasis on the significance of dielectric dispersion, fluorescence polarization, and x-ray methods. The hope of obtaining fairly rapidly a much deeper insight into protein structure now appears justifiable.