Researcher Database

（Last updated : 2024-08-01 16:03:58）　

KITAZAWA SOICHIRO

Department / Course College of Pharmaceutical Sciences Department of Pharmaceutical Sciences

Title / Position Assistant Professor

Academic background
1.	～2014/09	Doctoral Program (2nd Semester) │ General science and engineering │ Science and engineering │ Ritsumeikan Univ. │ Completed Doctor of science
2.	～2009/03	Applied Chemistry │ Science and Engineering │ Ritsumeikan Univ. │ Graduated
3.	～2011/03	Doctoral Program (1st Semester) │ Science and engineerign │ Science and engineering │ Ritsumeikan Univ. │ Completed

Business career
1.	2016/04/01	│ College of pharmaceutical sciences, │ Ritsumeikan Univ.
2.	2015/10/01 ～ 2015/11/30	│ Research organization of science and technology │
3.	2015/02/15 ～ 2016/03/15	│ │ Center for biotechnology and interdisciplinary studies, Rensselaer polytechnic insititute

Research activities
1.		The Nuclear Magnetic resonance society of japan

Subject of research
1.	Correlation Study on Structural Fluctuation Function of Phosphorylated Ubiquitin by High Pressure NMR Method

Research summary
If PINK1 and Parkin, Thr/Ser kinase, disfunction, abnormal mitochondria accumulate and Parkinson's disease develops. Ubiquitin (UB) is phosphorylated at S65 by PINK1. Phosphorylation UB(pUB) and Parkin's phosphorylation UB-like domain (pUBL) activate Parkin, an E3 ligase, and are associated with quality control of mitochondria (Iguchi et al. JBC 2013, Koyano et al. Nature 2014). Interestingly, phosphorylation-mimicking mutants S65D and S65E bypass PINK1 and activate Parkin (Koyano et al. Nature 2014). For crystal structure of pUB-Parkin complex, RING0 domain with self-inhibitor activity is removed and C431, the center of Parkin's activity, is exposed (Wauer et al. Nature 2015). This supports Parkin activation mechanism model proposed by Koyano et al. and draws attention to clarification of pUB-Parkin's interaction mechanism. Interestingly, pUB has two conformations, approximately at a ratio of seven to three and has structural fluctuation (Wauer et al. EMBO 2015, Fig. 1). X-ray crystal structure analysis shows that the Major structure of pUB is almost same as that of non-phosphorylation UB. On the other hand, for an atomic coordinate in the Minor state, chemical shift value analysis, analysis of hydrogen-bond pair and other analyses show that hydrogen-bond pattern slides for two residues between b5-strand and b1-strand/b3-strand. These b-strands form hydrophobic patches on the UB surfaces, and are the center of activity that interacts with a lot of proteins. Therefore, it is expected that it will effect intermolecular interactions or poly-UB. What interests you is that the pUB structure of pUB-Parkin complex is almost same as the Major structure. With a simple protein-protein interaction model called "key and keyhole model," it leads to expectation that the Minor state involving structural change will inhibit formation of complex, and the functional reason for its existence lacks in reasonableness. It is expected that clarifying structural fluctuation of UB and interaction mechanism of pUB-Parkin will lead to identify Parkinson's disease inhibitor mechanism through quality control of mitochondria. 　It has been discovered that UB has structural fluctuation on a wide time scale. There is a lot of uncertainty about relevance between that and function occurrence mechanism such as turning into poly-UB and ATP-dependent protein dissolution. Discovery of the mechanism, by which UB is phosphorylated by PINK1 and Parkin is activated by pUB, has triggered not only clarifying Parkinson's disease occurrence mechanism, but also drawing attention to UB's structural fluctuation and study of functional correlation. High pressure NMR method by an applicant is a powerful technique in which conformation equilibrium is significantly changed and measurement is allowed with one atomic resolution, even if probability of existence is only a few percents. Therefore, it is appropriate for study of the Minor state of pUB with low probability of existence or study of conformation of phosphorylation-mimicking mutants. 　If phosphorylation-mimicking mutants are discovered in the Minor state, it will imply how important the Minor state should be in molecular recognition mechanism of Parkin. Furthermore, we will identify the functional significance by comparing poly-UB chain formation by Parkin between pUB and phosphorylation-mimicking mutants.

Present specialized field
Molecular biology, Structural biochemistry, Biophysics, Physical pharmacy, Drug development chemistry (Keyword：Structural biology, Structural fluctuation, NMR, Protein)

Papers
1.	2019/09	Paramagnetic relaxation enhancement-assisted structural characterization of a partially disordered conformation of ubiquitin │ Protein science │ 29,pp.1993-2003
2.	2019/08	Pressure accelerates the circadian clock of cyanobacteria │ Scientific Reports │ 9,pp.12395
3.	2019/05	Gene delivery to cone photoreceptors by subretinal injection of rAAV2/6 in the mouse retina. │ Biochemical and Biophysical Research Communications │ 515,pp.222-227
4.	2018/09	Water-Protein Interactions Coupled with Protein Conformational Transition. │ Biophys J │ 18 (115),pp.981-987
5.	2017/08	Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin. │ Molecules │ 22 (9),pp.E1414
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