・ Membrane protein structural biology
The cell membrane is not only an envelope or a permeability barrier for the cell, but also the right place for certain biological reactions , like membrane transport, energy metabolism and signal transduction. There are a lot of proteins in the membrane, and they play physiologically important roles.
In our laboratory, we seek to understand the molecular mechanism of key biological processes on the cell membrane at the level of protein structure, dynamics and molecular biology. We keep challenging resolutely though it is known that structural analysis of membrane proteins is a very arduous field of science.
・ Membrane transport mechanism
Membrane transport is a fundamental biological process that is mediated by various transporter proteins.They incorporate materials necessary for the cell and export drugs or noxious compound out the cell.
We successfully solve the crystal structure of multi-drug efflux transporter in 2002 (FIGURE 1). This is the first accomplishment in the world for crystal structural analysis of the membrane transporter.
This kinds of protein export wide variety of drugs from the cell, and causes multi-drug resistance. This system is also known as the most basic host defense mechanism at the cellular level. These not only the cause of the multidrug-resistance for the pathogenic bacteria and the cancer cell but also bearing various cellular functions has understood recent years. MacB, a macrolide efflux transporter, also exports virulence factor of pathogenic bacteria (FIGURE 2). We are advancing the research aiming solving the protein structure, the molecular mechanism of the membrane transporter, and their cellular functions.
FIGURE 1 : Crystal Structure of Bacterial Multi-Drug Efflux Transporter AcrB
FIGURE 2 : Crystal Structure of Macrolide Efflux Transporter MacB
・ X-ray crystallography
Understanding of molecular mechanism of proteins based on their structures at atomic resolution is our major research object. For structural analysis of protein molecule - in particular for membrane proteins - X-ray crystallography is the most powerful technology.
Although membrane proteins are very tough target for X-ray crystallography, we are also trying to develop new techniques to challenge these targets having difficulty in crystallographic analysis, including an efficient purification methods and an new crystallization method.