240 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1950 



mechanism in the cell contain the same polypeptide chains as the 

 normal globulin and differ from normal globulin and each other only 

 in the configuration of the chain, that is, in the way the chain is coiled 

 in the molecule. It is much easier to devise a mechanism for causing 

 the polypeptide chain to assume the desired one of the alternative 

 configurations than to devise a mechanism for producing great varia- 

 tions in the ordering of the amino acid residues. Moreover, the num- 

 ber of configurations accessible to a polypeptide chain containing a 

 thousand or more amino acid residues is so great as to provide an ex- 

 planation of the ability of the animal to form antibodies capable of 

 specific combination with a very great number of different antigens. 



Let us assume that a portion of a polypeptide chain (one end, say) 

 which would be involved in the formation of a combining region of 

 the antibody is of such a nature that it is able to coil into any one of 

 a large number of alternative configurations, all of which have very 

 nearly the same energetic stability, so that the choice among them 

 may be determined by relatively small changes in the environment, 

 tending to stabilize one or another of the configurations. In the 

 absence of an antigen the polypeptide chain would fold into the con- 

 figuration that happens to be the most stable in the environment in 

 the cell, and would produce a molecule of normal y-globulin. In the 

 presence of the antigen, however, the folding of the polypeptide chain 

 would take place in a way determined to some extent by the interaction 

 of the chain with the atoms in the surface of the antigen molecule. 

 This interaction would find expression in the formation of that con- 

 figuration or those configurations of the polypeptide chain that permit 

 the system as a whole to have the greatest stability. The greatest 

 stability results, of course, from the formation of the strongest bond 

 between the folded polypeptide chain and the antigen molecule. 

 Accordingly, we have in this simple mechanism, involving the folding 

 of a polypeptide chain into a structure whose nature is determined 

 in considerable part by the presence of an antigen in the immediate 

 neighborhood, a straightforAvard way of producing an antibody 

 molecule with the power of specific combination with the particular 

 antigen present, resulting from a complementariness in structure 

 that is automatically assumed by the polypeptide chain that constitutes 

 the combining region of the antibody molecule. 



It is clear that the same mechanism, whereby one molecule present 

 in the cell may influence the structure of another molecule that is 

 being formed, may be invoked as an explanation of both hetero- 

 catalytic and autocatalytic activities of biological molecules in gen- 

 eral. A gene may have the power of causing the synthesis of a certain 

 protein molecule capable of acting as an enzyme catalyzing a particu- 

 lar chemical reaction through its possession of a structure essentially 

 complementary to that of the active region of the enzyme molecule, 



