284 CELL HEREDITY 



thousand Angstroms. One would expect that thov must he folded in 

 some orderly way to avoid a tangled chaos witliin the cell, and this is 

 indeed the case. The soluble proteins of the cells are approximately 

 globular in form, as the result of folding of the polypeptide chains into 

 specific three-dimensional configurations. These folded molecules ex- 

 hibit the binding affinities, activities, and serological specificities which 

 we measure. The folded configuration is presumablv quite stable and 

 uniform for each protein in any particular environment; physical and 

 biochemical studies indicate considerable homogeneity. 



What is known of the relationship between amino acid sequence and 

 folding? hi considering this problem, protein chemists have proposed 

 the following useful terminology: 



Primary structure refers to the order of peptide-bonded amino acid 

 residues along the polypeptide chain. Some investigators include here 

 the chemical cross links such as disulphide and phosphoester bridges 

 between segments of the same or different polypeptide chains. 



Secondary structure refers to the geometric arrangement of individual 

 polypeptide chains, determined by the backbone peptide configuration 

 and stabilized by interactions of the amino acid side chains. Best known 

 is the a-helix described bv Pauling et al.. and shown in Figure 10.5. A 

 polypeptide in a-helical configuration is rather a rigid rod; bending can 

 be occasioned by proline which does not fit into the tightly folded helix; 

 and possiblv bv other bulky aromatic amino acids like trvptophane, 

 phenvlalanine, and tvrosine. 



Tertiary structure refers to the final folded configuration of the protein 

 including spatial relations between neighboring segments of the same or 

 different polypeptide chains, which result from the combined force of 

 many interactions between side chains, bonds involving metals such as 

 zinc in insulin, electrostatic attractions, and various unspecified hvdrogen 

 bonds. 



So far as is known, enzymatically active proteins are in a folded or 

 "native" configuration. Consequently, the secondary and tertiary struc- 

 tures are most relevant to considerations of biological activity. Recently, 

 the term quaternary structure has come into use to denote aggregated 

 subunits, for example, the four polvpeptide chains of hemoglobin. The 

 state of aggregation mav also influence biological activitv. 



Protein chemists are investigating the question. To what extent does 

 the primary structure determine the folded configuration of the protein 

 in any particular environment? With the development of new analytical 

 techniques, it has become possible to determine the amino acid .sequence 

 of an entire protein, and thereby specify completely the primary struc- 



