PROTEIN STRUCTURE 



B) molecules (65). The peak distribution in the vector structure 

 (Patterson series) suggests that each 12,000 unit is made up of 

 four cylindrical rods of high electron density stacked in close- 

 packed array parallel to the a axis. The intermolecular packing 

 between these 12,000 molecular weight units maintains the 

 parallel close-packed arrangement throughout the structure. 

 The a axis in the air-dried crystals is 44 A long and thus the 

 maximum possible length of each rod is 44 A. It appeared 

 reasonable therefore to identify each cylindrical region with a 

 length of coiled or folded polypeptide chain. From calculations 

 based on the length and cross-packing area of each rod, the 

 density, and the number of residues in the B chain, it appears 

 that an a-helix might be the most plausible model for the chain 

 configuration (66,67). 



In suggesting this relationship Low observed that the 

 length of the B chain with 30 residues would, when coiled into 

 an a-helix configuration, be 45 A (30 X 1.5). In this crystal 

 structure model each crystallographic length of chain would 

 correspond to a complete A or B chain with parallel interchain 

 packing both within and between molecules. 



The a-helix structure satisfied the simple geometrical pack- 

 ing requirements of the unit cell. It appeared useful therefore 

 to undertake a scale model study based on the Sanger amino 

 acid sequences. An early model study established that in the 

 two-chain (A + B) unit a simple model of parallel a-helices for 

 both A and B chain required modification. The — Cj^) — S — 

 (half cystine) residues on the As and A^ a-carbon positions are 

 too far removed in space on a simple a:-helix structure to permit 

 the formation of an A"] intrachain disulfide bond. 



A simple continuous a helix structure is thus ruled out for 

 the A chain of insulin. This limitation does not impose intrinsic 

 restrictions on the configuration of the terminal segments of the 

 A chain. Both these two parts of the A chain and the whole of 

 the B chain may be in the a-helix configuration without 

 aff'ecting the interchain cystine linkages. If the specific con- 

 figuration of the pentapeptide loop is irregular, then intrachain 



421 



