Structural and functional effects of pseudo-module substitution in hemoglobin subunits. New structural and functional...

Functional and structural significance of the "module" in proteins has been investigated for globin proteins. Our previous studies have revealed that some modules in globins are responsible for regulating the subunit association and heme environmental structures, whereas the module substitution often induces fatal structural destabilization, resulting in failure of functional regulation. In this paper, to gain further insight into functional and structural significance of the modular structure in globins, we focused upon the "pseudo-module" in globin structure where boundaries are located at the center of modules. Although the pseudo-module has been supposed not to retain a compactness, the betaalpha(PM3)-subunit, in which one of the pseudo-modules, the F1-H6 region, of the alpha-subunit is implanted into the beta-subunit, conserved stable globin structure, and its association property was converted into that of the alpha-subunit, as the case for the module substituted globin, the betaalpha(M4)-subunit. These results suggest that modules are not unique structural and functional units for globins. Interestingly, however, the recent reconsideration of the module boundary indicates that the modules in globins can be further divided into two small modules, and one of the boundaries for the new small modules coincides with that of the pseudo-module we substituted in this study. Although it would be premature to conclude the significance of the modular structure in globins, it can be safely said that we have found new structural units in globin structure, probably new modules.