Research Theme
Structural basis for maintenance of DNA methylation and its application.
- Name
- Kyohei Arita
- Position, Research site
- Associate Professor, Graduate School of Medical Life Science, Yokohama City University
Maintenance of DNA methylation plays an important role in regulation of the function and morphology of cells. In this study, I introduce the time course, namely cell cycle, into the research of structure biology field. The aim of this study is revealing the regulation of alteration of protein structure and function depending on the cell cycle to obtain the molecular mechanism of maintenance of DNA methylation. In addition, I also reveal a novel regulation of enzymatic activity of maintenance DNA methylatraseferase to achieve the mechanism of DNA methylation maintenance.
Structural and functional study of Mediator CDK module
- Name
- Tsuyoshi Imasaki
- Position, Research site
- JST/PRESTO Researcher(Center for Life Science Technologies(CLST), Riken)
Mediator is a multi-protein complex, which transduces activator signal to the RNA polymerase II transcription machinery. CDK module is a module of the Mediator, plays essential role in transcription regulation by its kinase activity and interaction with their binding partners. It is known as a potential drug target for cancer and neurological disorders. In the proposed research, I aim to reveal transcription regulation mechanism of the CDK module by X-ray crystallography and biochemical approach.
Unveiling molecular mechanisms of chaperone network mediated by transient complexes
- Name
- Tomohide Saio
- Position, Research site
- Assistant Professor, Structural Chemistry Lab., Division of Chemistry, Graduate School of Science, Hokkaido University
Protein folding and translocation are mediated by many proteins including molecular chaperones. Despite of their important roles, molecular mechanisms of chaperones are poorly understood. Especially the knowledge on detailed mechanisms of their substrate recognition and network is limited. Dynamic and transient interaction between chaperone and its substrate as well as between chaperones makes crystallographic approach difficult. Here we primarily exploit modern NMR to unveil detailed mechanisms of molecular chaperones by integrated analysis of structure, dynamics, and interactions.
Structural and biochemical analysis of Vesicular glutamate transporter
- Name
- Narinobu Juge
- Position, Research site
- Assistant Professor, Advanced Science Research Center, Okayama University
Vesicular glutamate transporters (VGLUTs) are responsible for the vesicular storage of L-glutamate and play an esssential role in glutamatergic signal transmission in the central nervous system.The molecular mechanism and crystal structure of the transport remains unknown. I will provide the structural and functional insights on VGLUT.
Dynamic structural analysis of multidrug resistance based on panspecific molecular interactions
- Name
- Koh Takeuchi
- Position, Research site
- Senior research scientist, Molecular Profiling Reasearch Center for Drug Discovery, National Institite of Adnanced Industrial Science and Technology
The acquisition of multidrug resistance (MDR) by pathogenic bacteria and cancer is a major threat in current medication. To overcome this issue, understanding of the molecular mechanism of MDR is of importance. The research focuses on the multidrug transcriptional regulators (MDTRs), which represent high affinity sensors in the MDR system, and reveal the structures of MDTRs in complex with drugs and DNA as well as their functional dynamics by using solution-NMR techniques. The research will establish a fundamental knowledge that can be expanded to the transcriptional regulation in general, which would also indicate the way to overcome the MDR issues.
Elucidation of dynamical structures of membrane voltage sensor
- Name
- Kohei Takeshita
- Position, Research site
- Visiting Academic Staff (Specially Appointed Assistant Professor), Laboratory of Supramolecular Crystallography, Institute for Protein Research, Osaka University (Interdisciplinary Program for Biomedical Science, Institute for Academic Initiatives, Program for Leading Graduate Schools)
Membrane potential is essential in many biological functions, such as neural signal transduction, muscle con¬traction and secretion and so on. Membrane voltage sensor is important for responses upon membrane potential changes. Voltage sensing protein family is the key protein family for membrane potential responses. The voltage-gated proton channel permeate proton depending on membrane potential changes. It is the most compact voltage sensor protein suitable for understanding essential function of voltage sensor. The outcome of the research will lead to understand the dynamical mechanism of membrane voltage sensor from structural studies of voltage-gated proton channel.
Analysis of protein domain dynamics by integrating of neutron scattering and computer science
- Name
- Hiroshi Nakagawa
- Position, Research site
- Assistant Principal Researcher, Sector of Nuclear Science Research, Japan Atomic Energy Agency
Elucidating domain fluctuation as a structural unit is necessary to understand the molecular basis of structural polymorphism and plasticity of proteins, which interact with various molecules. In this study, I will develop a correlative structural analytical method by integrating neutron scattering experiment data and computational analysis to obtain information on domain motion at the atomic level. Moreover, by applying this technique to cytokine receptors, I will elucidate the activation mechanism controlled by the structural changes.
Structual studies of membrane protein complex
- Name
- Tomohiro Nishizawa
- Position, Research site
- Assistant Professor, Graduate School of Science, The University of Tokyo
Most integral membrane proteins are assembled into functional complexes in biological membranes, wherein homo- and heterophilic protein interactions are formed in the lipid environment. Structural information of these biological assembly are necessary to understand the moleculalr mechanism of their functions. In this research, lipidic cubic phase crystallization and cryo-electron microscopic analysis are employed for obtaining entire structure of the membrane protein complexes. The goal of the research is to elucidate the celllular function of these membrane protein complexes.
Efficient membrane protein crysatllography by using ultra-thin membrane at synchrotron and XFEL facilities
- Name
- Kunio Hirata
- Position, Research site
- Senior technical scientist, RIKEN/SPring-8 Center
Protein crystallography is one of the key techniques for acquiring precise structural information of protein for understanding its biological function. Recent micro-focus X-ray beam available at synchrotron and XFEL facilities enable membrane protein crystallography with micron-sized crystals. Moreover at XFEL facilities, radiation damage free structure analysis can be achieved. Though many tools and methods for mounting crystals to X-ray path have been developed, there are rooms to be considered so that high resolution data collection can be accomplished more quickly. A 'graphene' membrane is a potential candidate which can solve the problems. Developing new methodologies of preparing/mounting a plenty of membrane protein crystals with isomorphisms with graphene membarane are proposed. This development is aimed to achieve high resolution/high throughput membrane protein crystallography, high resolution time-resolved damage free structure analysis of membrane protein.
Dissection of the circadian clock machinery by integrating structural biology and chemical biology
- Name
- Tsuyoshi Hirota
- Position, Research site
- Designated Associate Professor, Institute of Transformative Bio-Molecules (ITbM), Nagoya University
The circadian clock controls the daily rhythms of a variety of physiological processes. To understand the molecular nature of the circadian clock system, this project aims to reveal regulatory mechanisms of clock proteins and enable strict control of their functions. The clock-regulating compounds that the applicant has discovered will be used as a tool in combination with structural biology approaches to address fundamental questions of the circadian clock: how the clock works in a very precise manner, and how it regulates physiological processes.