A distance matrix is a set of genetic distances between all possible pairs of proteins under consideration, and is used to construct a phylogenetic tree by the distance matrix method. Pazos and Valencia (2001) have developed a method to predict protein-protein interaction by evaluating the similarity of the distance matrices, under the assumption that the phylogenetic trees of interacting proteins resemble each other through co-evolution. It is known, however, that the prediction includes many false positives. We postulated that the cause of the false positives is the background similarity of the phylogenetic relationship of the source organisms. We have developed a method to exclude such information from the distance matrices with a projection operator. The number of false positives was drastically reduced from the prediction by evaluating the similarity between the residuals after the projection operation.
Aggregation of proteins is a serious problem, affecting both human health and industrial production of proteins. We have recently succeeded in showing that association and dissociation of amyloid protofibrils can be controlled reversibly with pressure and the protofibril formation is a slow process toward thermodynamic equilibrium. Extensive studies have recently been carried out also by other workers on dissociation of oligomer/aggregate of proteins using high pressure. This article reviews the current progress of such studies including dissociation of amyloid fibrils and refolding from inclusion bodies. These studies show that pressure is one of the useful tools for controlling protein dissociation and association reaction.
In the inner ear, hair cells detect not only sounds but also acceleration with their mechanotransduction apparatus. In this study, I demonstrate that transduction and adaptation require phosphatidylinositol-4,5-bisphosphate (PIP2) for normal kinetics. PIP2 has a striking distribution in hair cells, being excluded from the basal region of hair bundles and apical surfaces of bullfrog saccular hair cells. The depletion of PIP2 by the inhibition of phosphatidylinositol 4-kinase or sequestration by an aminoglycoside reduces the rate of fast and slow adaptation, and also causes a loss in transduction currents, suggesting that PIP2 plays an essential role in hair cell adaptation and transduction.
A G-quadruplex DNA is composed of stacked G-quartets, each of which involves the planar association of four guanine bases. The size and planarity of a G-quartet are well-suited for interacting with a porphyrin ring through π-π stacking. We have demonstrated the formation of a stable coordination complex between heme, the iron (III)-protoporphyrin IX complex, and a parallel G-quadruplex DNA assembled from a single repeat sequence of the human telomere, TTAGGG. The heme-DNA complex was found to be remarkably similar, in various spectroscopic and functional properties, to hemoprotein such as myoglobin.
The development of a multicellular organism is a dynamic process. With the increase of the cell number, starting from one or a few cells, cells are differentiated with different compositions. These differet types of cells form an ordered pattern. It is rather surprising that differentiation in cell types and formation of controlled patterns are compatible, because the former gives morphogenetic diversification whereas the latter implies recursive production of a cell ensemble, reducing individual differences. We studied this problem by taking a simple cell model with intracellular reaction dynamics of chemical concentrations, cell-cell interactions, and increase in cell numbers. We show that, by starting from an initial object consisting of both the cell type with diverse chemicals and the differentiated cell type, the recursive production of a multicellular organism with morphogenetic diversity is possible.
The structural based drug-design (SBDD) is one of the useful methods for producing a novel medicine. We recently succeeded in X-ray crystallographic determination of two target molecules. One is human hematopoietic prostaglandin (PG) D synthase (H-PGDS) that produces PGD2 as an allergic mediator in mast cells and Th2 cells. The other is Trypanosoma brucei PGF2α synthase (TbPGFS), a member of the aldo-ketoreductase superfamily, catalyzes the NADPH-dependent reduction of PGH2 to PGF2α, whose overproduction during trypanosomiasis causes miscarriage in infected female subjects. In this report, we introduce the recent progress in the research of the high resolution structures of human H-PGDS and TbPGFS useful for SBDD.