NATURE Facts and Theories Tn Protein Chemistry*
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No. 3606, DEC. 10, 1938 NATURE 1023 Facts and Theories tn Protein Chemistry* JN the last decade, many investigations of an Viscosity measurements on anisotropic proteins exact nature have been made on the proteins may be correlated with the axial ratios of the in solution and in the solid phase. Unfortunately, corresponding molecular ellipsoids of rotation by by a dissipation of the available research energy means of equations proposed independently by among a wide variety of proteins and by a signal Kuhn, Burgers and Polson. From the axial ratio absence of co-operation among the researchers the molecular frictional coefficient may be cal themselves, less significant advances have been culated, and this in turn supplies the necessary made in the elucidation of fundamental principles information for calculating molecular weights from than would otherwise have been the case. It was diffusion data. Molecular weights thus obtained a happy inspiration, therefore, which brought from viscosity and diffusion data agree with the together most of the authorities on protein ultracentrifuge values only when Polson's equa chemistry in Europe at the Royal Society on tion, which has a purely empirical basis, is used. November 17 to compare their experiences and Studies on the peptic digestion of egg albumin discuss each other's difficulties. by Tiselius show that the decomposition products Prof. The Svedberg (Uppsala) opened the con have a much lower electrophoretic mobility than ference with a vigorous and notably wide survey the uncharged protein. This supports the view of recent developments in the physical chemistry that the constituent units of a protein particle are of the proteins. According to precise physical bound together by specific chemical linkages and measurements, protein particles have such char that the particle is in fact a single molecule. acteristic and reproducible properties that it is no Recent theories of protein structure proposed by longer possible to deny them the right of classifica Wrinch and by Bergntann and Niemann imply the tion as giant molecules. Sedimentation studies on chemical individuality of the protein molecule. native soluble proteins reveal a striking homo These theories are important as a stimulus to geneity in the sizes of individual molecules, and further research ; but caution must be observed in the method of electrophoresis reveals a similar their acceptance. In the case of Bergmann and homogeneity in their free charges. Measurements Niemann's theory, which assumes a fundamental of protein molecular weights by sedimentation regularity in the arrangement of the amino-acid equilibrium or by a combination of sedimenta residues in the molecule, certain difficulties exist. tion velocity and diffusion give values which, For example, the theory gives a molecular weight rather unexpectediy, conform to a law of simple of 69,000 for hremoglobin based on a cysteine multiples. content of 0·5 per cent and assuming three Assuming 17,600 as the unit of molecular weight, cysteine residues per molecule. Ultracentrifugal the values of some sixty native proteins so far and X-ray methods show, however, that bremo investigated, including the giant hremocyanin globin may be split reversibly into halves of molecules with weights of several millions, may approximately equal size. be expressed as multiples of this unit by factors Dr. Linderstram-Lang (Copenhagen) emphasized containing powers of 2 and 3. The rule is approxi the value of enzymic degradation as a method of mate only, suggesting the existence of some under studying the structure of the protein molecule, lying architectural principle in the arrangement especially in recent years with the advent of of the amino-acid residues. Differences in the crystalline and relatively pure enzymes. Consider percentage amino-acid composition of proteins able care is still required in the interpretation of may explain the spread of molecular weights above the results of these studies, since it is now becoming and below the simple multiple value. Determina clear that some fundamental change scarcely tions of osmotic pressure give values which agree distinguishable from denaturation is a necessary well with molecular weights obtained by sedi preliminary to the enzymic disruption of poly mentation methods. X-ray investigations of pep peptide bonds in the protein molecule. Dr. D. sin, insulin, lactoglobulin and hremoglobin in the Wrinch (Oxford) gave a clear presentation with crystalline state have given valuef! of 40,000, the aid of models of her 'cyclol' hypothesis, which 37,200, 36,500 and 69,000 respectively, while the assumes that the protein molecule is constituted of ultracentrifuge gives 37,000, 38,000, 39,000 and diazine and triazine rings arranged alternately in 68,000. a kind of fabric which may be folded according to purely geometrical considerations. The space • Substance of a discussion on "The Protein Molecule" held by the Royal Society on November 17. enclosing fabric with 288 amino-acid residues takes © 1938 Nature Publishing Group 1024 NATURE DEC. 10, 1938, VoL. 142 the form of a truncated tetrahedron and this in fact they are about 100,000 in weight (Sw,2o·=6) represents the globular protein molecule of weight the absence of two boundaries might be explained 35,000. Dr. A. Neuberger (London) pointed out that by postulating an extremely mobile form of calcium the presence of diazine and triazine rings in pro casein equilibrium. teins is not supported by chemical facts. It has Prof. H. H. Weber (Munster) opened the after never been shown that a lactam-lactim tautomerism noon session with a paper on the proteins of exists in peptides, nor has a polymerization of muscle, dealing particularly with myosin. Solu peptides to cyanidine-like rings been realized. tions of this protein show a high and anomalous The chemical and enzymic behaviour of proteins viscosity and marked anisotropy of flow. Solutions is also not in accordance with the cyclol hypo more concentrated than 2 per cent cannot be thesis. The Bergmann and Niemann hypothesis obtained in the disorientated state, but orientated was also criticized by Dr. Neuberger on the grounds threads may be spun like artificial silk to much that the limits of error in the present methods of higher concentrations. These threads resemble estimating amino-acids are so great as to render muscle fibres closely in swelling power, tensile the deductions made from them statistically strength, elastic properties and X-ray appearances. of doubtful value. Measurements of the double refraction and the Dr. G.S.Adair (Cambridge) showed that for bromo eigendoppelbrechung of the stretched myosin thread globin, egg albumin and serum albumin, the maxi show that these correspond quantitatively with the mum values for the molecular radii calculated values for the Q-disks of muscle. The Q-disk con from measurements of diffusion made at Uppsala, sists therefore of fully orientated myosin rods. were not more than 5 per cent greater than the Complete elastic stretching of the myosin filament minimum values calculated from measurements of results from stretching of the rods themselves, the the hydration and density of protein crystals sus process consisting evidently in a straightening of pended in sodium phosphate buffers. He also dis folded filamentous molecules. Myosin may be cussed the effects which salts have on theiso-electric denatured by heating above 40° C., the threads points of proteins. Dr. K. 0. Pederson (Uppsala) undergoing an irreversible decrease in double described new work on the dissociation of proteins, refraction and a marked contraction. The view particularly the type of molecular splitting which is put forward that muscle contraction consists in one component of a binary mixture induces in the a chemically induced denaturation of myosin mole other. The dissociation is more marked when a cules which is reversible in the circumstances per carbohydrate-rich protein is mixed with a carbo taining to muscle. Dr. G. Boehm (Basle) showed hydrate-poor one. It is also marked in serum in a number of X-ray diagrams of stretched myosin which there is evidence that phosphatides take a threads. Prof. K. H. Meyer (Geneva) developed role similar to the carbohydrate. The X-fraction some interesting ideas on mechanically induced seen in the sedimentation diagram of normal molecular transformations, citing the solubility and serum is identical with the intermediate or (3- elastic changes caused in the crude material from globulin seen in electrophoresis, and this fraction the silk gland by simple stretching, and the according to Tiselius and Blix is the main carrier crystallization of metastable selenium by similar of the serum phosphatides. Changes which affect treatment. He is of the opinion that blood the serum calcium, for example, dialysis, addition plasma may be regarded as a supersaturated of 11alts, etc., affect the sedimentation rate of the fibrinogen solution and that mechanical denatura X-component. The effect is probably on the tion may suffice to explain the phenomena of phosphatide linkage. blood clotting. Dr. W. T. Astbury (Leeds) referred Dr. Pederson suggested that these and other to the elegant method of progressive piling of dissociation effects are best explained by postu protein monolayers on a metal slide until it is lating that the larger protein molecules consist of possible to measure the thickness of a monolayer small primary protein units linked into a secondary by means of a