Laboratory of Structural Biology

Research Outline

We have elucidated the basic mechanism of life phenomena using structural biology methods. Furthermore, we are creating a basis for designing more potent drugs that regulate the phenomena through the structural analysis of drug–target complexes.

Theme outline

1. Structural biology of autophagy

Autophagy is an intracellular degradation system conserved in eukaryotes. It has various physiological roles and its dysfunction causes various severe diseases such as neurodegeneration and cancer. During autophagy, doublemembrane structures called autophagosomes are generated, which sequester degradation targets and deliver them to the lytic compartment, the lysosome, where they are degraded by hydrolases. Over 40 Atg proteins have been identified as critical factors for autophagy; however, the molecular mechanism of how these Atg proteins mediate each process of autophagy remains to be elucidated. We are attempting to determine the molecular mechanism of autophagy through a comprehensive structural study of Atg proteins and a functional study based on structural information. Based on the structural and functional information obtained, we are developing drugs that regulate autophagy.

Fig.1 Atg protein structures that have been determined

2. Structural analysis of drug–protein complexes

We are performing structural studies of the physiologically active substances, which were developed in IMC, as a complex with their target proteins using X-ray crystallography. Based on the structural information of the compound–target complex obtained, we are elucidating the mechanism of action for the compounds and designing a new compound that has a higher affinity for the target protein. For example, we are using X-ray crystallography to determine the ternary complex formed between a new anti-MRSA (methicillin-resistantStaphylococcus aureus) drug, DNA gyrase, and DNA.

Fig.2 Rigaku VariMaX with RAPID
Fig.2 Rigaku VariMaX with RAPID
Fig.3 RIBM Nano Explorer High-Speed Atomic Force Microscopy
Fig.3 RIBM Nano Explorer
High-Speed Atomic Force Microscopy