3] CONFIGURATION OF GLOBULAR PROTEINS 61 



in aqueous solution. ^"•^^•" The extent of polymerization is lowest when 

 the molecule bears a high net charge, positive or negative. It increases as 

 the isoelectric point is approached, and, in the isoelectric region itself, leads 

 to insolubility of the protein. This is clearly the expected result if electro- 

 static forces predominate in the pH-dependence of intermolecular attraction. 

 Hemoglobin^^ is another globular protein which fits this picture. It exists 

 as a dimer near its isoelectric point and dissociates reversibly as the pH is 

 lowered. Dissociation is probably complete before the expansion earlier 

 referred to occurs. 



The most interesting example of the polymerization of a compact protein 

 molecule is that which occurs for j8-lactoglobuHn.^^'^"2.io3 Experimental 

 molecular weights for this protein, as observed by Townend and Timasheff, 

 are shown in Fig. 15. The most interesting feature is the polymerization of 



2 3 4 5 6 



pH 



Fig. 15. The molecular weight of iS-lactoglobulin near 25° (dashed line) and near 2° 

 (solid line) (Townend and Timasheff 102,103) . (j 25° at the lowest feasible concentration, 

 as determined by the Archibald method; Q 25°, miscellaneous observations; 2°, at 

 concentrations of 2 to 3 %, calculated from the relative areas of separate sedimentation 

 peaks representing species of molecular weight 35,000 and 70,000. The arrow locates the 

 isoelectric point. 



the dimer, at 0°C, which occurs entirely on one side of the isoelectric point. 

 These observations, coupled with the earlier observation that ^S-lactoglobulin 

 becomes randomly coiled on the alkaline side of the isoelectric point, and 

 not on the acid side, make this one of the most interesting of all globular 

 proteins. 



It might at first sight seem probable that globular proteins in a randomly 

 coiled configuration should be more liable to polymerization than the same 

 proteins in compact configurations. However, the forces, such as electrostatic 

 repulsion, which lead to the preference for a randomly coiled configuration, 



