Development of a method to predict protein function based on module classification

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The aim of this study is (1) to clarify that key components of protein functions are localized to compact short segments, modules, and (2) to elucidate principle of protein design using modules as building blocks. In consequence, we found various kinds of protein functions were assigned to modules. For example, (1) the functional sites of the catalytic domain of family 10 xylanase are localized to some of the modules; (2) in many case, ligands for certain metal ions exist within one or two modules. Furthermore, modules with similar structure and function are frequently observed in various proteins, which indicates the possibility that the modules were shuffled. In addition, (3) common modules are found to be used for protein-protein interaction; (4) only two modules are used in subunit interaction of hemoglobin, which could explain why subunit interactions of hemoglobin are diversified in various lineage. We also showed that modules can be deleted or shuffled by experiments. For example, (1) module M2 in barnase was deleted without loss of the stable three-dimensional structure similar to the native structure and the cooperative folding behavior. (2) a chimera xylanase, which was made by exchange of module M10 between two kinds of xylanases in family 10, maintained the structure and function, though the enzyme activity decrease by a tenth. This study has clarified a basic principle for module-based protein design from both views of computer science and experimental science.