Inaba K, Ishimori K, Imai K, Morishima I
Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8501 Japan.
J Biol Chem. 1998 Apr 3;273(14):8080-7. doi: 10.1074/jbc.273.14.8080.
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.
针对珠蛋白，人们已对蛋白质中“模块”的功能和结构意义展开了研究。我们之前的研究表明，珠蛋白中的一些模块负责调节亚基缔合和血红素环境结构，而模块替换往往会导致致命的结构不稳定，从而致使功能调节失效。在本文中，为了更深入地了解珠蛋白中模块化结构的功能和结构意义，我们聚焦于珠蛋白结构中的“假模块”，其边界位于模块中心。尽管假模块被认为不具备紧密性，但在βα(PM3)亚基中，α亚基的一个假模块（F1 - H6区域）被植入到β亚基中，它保留了稳定的珠蛋白结构，并且其缔合特性转变为了α亚基的缔合特性，就如同模块替换的珠蛋白βα(M4)亚基一样。这些结果表明，模块并非珠蛋白唯一的结构和功能单元。然而，有趣的是，最近对模块边界的重新审视表明，珠蛋白中的模块可进一步分为两个小模块，并且新小模块的其中一个边界与我们在本研究中替换的假模块的边界重合。虽然现在就得出珠蛋白中模块化结构的意义还为时过早，但可以肯定地说，我们在珠蛋白结构中发现了新的结构单元，可能是新的模块。
