158 THE BIOSYNTHESIS OF PROTEINS 



each synthetic antigen. It was deemed much more probable that the 

 antigen itself participates in the molding of the corresponding specific 

 antibody. 



Thus Breinl and Haurowitz (1930) advanced the view that the antigen 

 interferes with the process of globulin synthesis so that globulin molecules 

 complementarily adjusted to the shape of the specific groups of the antigen 

 are formed. Proteins can difter by the amino acid sequence in the chains 

 or (and) by the way these chains are folded. Pauling (1940) elaborated a 

 model of antibody synthesis in which it was assumed that the polypeptide 

 chains of the globulins or certain regions of them were likely to assume 

 many different types of folding. In the absence of an antigen molecule, the 

 newly synthesized polypeptide chain might fold up in any one of a number 

 of ways, representing the maximum stability under the conditions then 

 existent in the cell. If, however, an antigen molecule were present, the 

 polypeptide chain would fold up into a configuration complementary in 

 structure to the antigen molecule. The specific shape of the antibody mole- 

 cule would thus be imprinted upon the plastic polypeptide chain of the 

 globulin molecule by the antigen itself. 



It must be noted here that the structural information brought by the 

 antigen adds to the unchanged genetic information, and that it is of a 

 completely different nature. The additional information controls the estab- 

 lishment of the secondary and tertiary structures of the polypeptide only. 

 It is a kind of structural information which is disregarded in the present 

 concepts of protein synthesis in which all the attention is focused on the 

 primary structure of the protein (see p. 122). The antigen-template would 

 act after the nucleic acid template has assembled the amino acids into a 

 polypeptide in the genetically controlled sequence. 



The direct antigen template hypothesis has implications which could, 

 in principle, be checked experimentally. It assumes that the antigen must 

 be present for antibody production to continue; it predicts that all anti- 

 bodies, or at least many antibodies, should have the same amino acid 

 sequence. This prediction is amenable to experimental check. Five different 

 antibodies produced by the rabbit against ovalbumin and against four 

 strains of Pneumococcus respectively, all terminate by the same amino acid 

 sequence Ala-Leu-Val-Asp-Glu and four more antibodies which have not 

 been studied as thoroughly also have a terminal Ala (Porter, 1950a; 

 McFadden and Smith, 1955). Within experimental limitations, the amino 

 acid composition is the same for all (Smith et al., 1955). These facts lend 

 support to the above hypothesis. It should not be overlooked, however, that 

 the globulins are large molecules containing some 1500 amino acid 

 residues and that the replacement of a few amino acids by others would 

 not be detected easily. But the techniques for determining the amino acid 

 sequence have advanced considerably in the last few years, and it is to be 



