1 



Factors affecting the structure of hemoglobins 

 and other proteins 



LINUS PAULING 



and Crellin Laboratories of Chen 

 a Institute of Technology, Pasader 



(Communication No. 2215) 



Gates and Crellin Laboratories of Chemistry 

 California Institute of Technology, Pasadena, Caüf. 



An understanding of the structural basis of the difference in properties of 

 normal adult human hemoglobin and the abnormal hemoglobins, such 

 as sickle-cell-anemia hemoglobin, will be obtained only when complete 

 structure determinations of the molecules of these substances have been 

 made. The properties of hemoglobin depend not only on the sequence of 

 amino-acid residues in the polypeptide chains but also on the way in which 

 the polypeptide chains are folded. 



It is probable that the folding of the polypeptide chains of a protein is 

 in considerable part, perhaps in some cases entirely, determined by the 

 amino-acid sequence in the chains. For example, it has been shown by 

 Doty, Moffitt, and their co-workers^ -^-^ that the chains of poly-a-L- 

 glutamic acid and of poly-y-benzyl-L-glutamate have the configuration, in 

 solution in certain solvents, of the right-handed a-helix, and that the mole- 

 cules resume this right-handed helical configuration after they have been 

 unfolded by change in the nature of the solvent, and then have been re- 

 turned to the original solvent in which the a-helix is stable. It is evident 

 that the interactions of the side chains of the L-amino-acid residues stabilize 

 the right-handed a-helix relative to the left-handed a-helix for these poly- 

 peptides. Yang and Doty^ have also reported that the molecules of certain 

 proteins — especially silk fibroin and the B chain of insulin — can, in certain 

 solvents, be brought into the configuration of the right-handed a-hehx. 

 These assignments of sense to the a-helix, made by application of the theory 

 of optical activity developed by Moffitt,^ are probably more reliable than 

 the earher assignments made by Riley and Arndt. ^ 



There is a possibihty that the difference in properties of the abnormal 

 hemoglobins and normal adult human hemoglobin can be ascribed en- 

 tirely to the replacement of a few amino acid residues by residues of other 



Bps 



