differentiation and protein synthesis 119 



Secondary and Tertiary Structures 



While a partial answer to the problem of peptide formation seems in 

 sight, a more formidable problem yet to be solved is that of specificity, i.e. 

 the formation of precise sequences of amino acids in the polypeptide chain 

 and the folding of these chains into equally precise three-dimensional 

 structures. Whether keratin, a protein whose function is a more or less 

 passive mechanical one, will actually prove to have a specificity as clearly 

 defined as an enzyme has not yet been proved by an actual determination 

 of an amino acid sequence. It is, however, antigenic (Pillemer et al., 1939 

 and 1938) and in well-crystalline forms (feather and porcupine quill) it 

 yields an X-ray pattern suggesting a complexity not inferior to that of 

 soluble proteins (Chapter 5). 



Following a suggestion by Haurowitz and by others, it seems reasonable 

 to think that the final assembly of amino acids takes place in two steps: 

 (1) the formation of the definite polypeptide sequence (or sequences) on a 

 template and (2) the folding of the polypeptide to form a three-dimensional 

 molecule (Fig. 51, Steps 4 and 5). The attack on this problem is at the 

 moment largely speculative. Most writers assume that the sequence of 

 bases along a nucleic-acid helix somehow ultimately determines the 

 sequence of amino acids, and attempts to solve the problem, ranging from 

 biochemical experiments to abstract considerations based on coding theory, 

 are being made. The general feeling is that the microsomal RNA is the 

 most likely candidate for a template on which to assemble the amino acids 

 in the correct order and Crick has advanced further arguments to show 

 that an " adaptor molecule " is also necessary to hold the activated amino 

 acid on the template. In the absence of experimental evidence it is not 

 easy to carry this discussion further, but reference may be made to Crick's 

 article (1958). 



The problem of the second step, the folding of the long polypeptide 

 chain into a specific configuration and the overall shaping of the molecule, 

 has been illuminated experimentally by the work on the lability of protein 

 configurations in solution and the dependence of both synthetic and 

 natural polypeptides on the interaction between the solvent and the chain. 

 This work will be returned to later (p. 194). What is important is that this 

 step seems to require no enzymatic or nucleic acid intervention; it 

 depends simply on the energy relations of the interactions between side 

 chains of the macromolecule and the molecules of the solvent or other 

 associated molecules Since the side-chain composition of a polypeptide 

 chain is determined in the primary act of synthesis (assembly on a tem- 

 plate) the configuration ultimately assumed by the molecule in a given 

 medium (cell sap) will be determined at the same time and by the same 

 means. 



