12] STRUCTURE OF RIBONUCLEASE 221 



visualize the ribonuclease molecule in the two-dimensional schematic repre- 

 sentation shown in Fig. 6. It is quite clear that the protein must exist in a 

 tightly wound folded form. It should be noted that the small disulfide ring 

 around the IV-V disulfide bond, is two residues larger than the small ring 

 already found in insulin by Sanger and in vasopressin and oxytocin by 

 du Vigneaud and his colleagues. 



The information contained in Figs. 2 and 6 furnishes as complete a pic- 

 ture of the covalent structure of the ribonuclease molecule as can be drawn 



NH, 



3lS 



S . ^COOHI 



S 



2 



Fig. 6. A two-dimensional diagram indicating the positions of the four disulfide bonds 

 in native ribonuclease. (Based upon the results of Spademan et al.^^ and Ryle and Anfinsen.^^ ) 



now. The studies outlined in this communication encourage the hope, how- 

 ever, that the complete elucidation of the structure is not too far off. Although 

 this appears to be a straightforward task, the protein chemist must always 

 be on the look-out for unsuspected types of linkages in proteins. Such 

 linkages have been found in bacitracin by Craig and his colleages,^" and 

 by Newton and Abraham, ^^ and recently in collagen by Mechanic and 

 Levy. 22 It is becoming increasingly clear also that even a complete know- 

 ledge of all of the covalent linkages in ribonuclease will almost certainly 

 not mean that the chemical, enzymatic, and physical properties of the pro- 

 tein will automatically be understood. Indeed, it appears as though detailed 

 structural knowledge frequently does not actually solve problems, but rather 

 permits the problems to be rephrased in different, albeit more precise, terms. 

 Possibly it is one of the functions of a symposium such as this to draw 

 attention to those areas of protein structure that lie beyond the detailed 

 formulae that we all are so happily constructing at the present time. 



REFERENCES 



1. s. MOORE and w. h. sj^i-h, Harvey Lectures, Stx'ics 51, 119(1956-57). 



2. c. H. w. HiRS, w. H. STEIN and s. MOORE, J. Biol. Chem., 221, 151 (1956) 



3. F. SANGER, Bull. Soc. chwi. BioL, 37, 23 (1955). 



