研究者詳細

顔写真

キノシタ　ミサキ
木下　岬
Misaki Kinoshita
所属
高等研究機構学際科学フロンティア研究所　新領域創成研究部　先端基礎科学研究領域
職名
特任助教（研究）
学位

  • 博士(理学) （大阪大学）

e-Rad 研究者番号
10823809

経歴 4

  • 2026年4月 ～ 継続中
    東北大学 学際科学フロンティア研究所　特任助教

  • 2021年4月 ～ 2026年3月
    一般社団法人 日本血液製剤機構

  • 2020年8月 ～ 2021年3月
    バイオ科学株式会社

  • 2018年4月 ～ 2019年12月
    東北大学　学際科学フロンティア研究所　学術研究員

学歴 3

  • 大阪大学大学院　理学研究科　生物科学専攻

    2015年4月 ～ 2018年3月

  • 大阪大学大学院　理学研究科　生物科学専攻

    2013年4月 ～ 2015年3月

  • 大阪大学　理学部　生物科学専攻

    2009年4月 ～ 2013年3月

所属学協会 3

  • 日本生物物理学会

  • 日本蛋白質科学会

  • 日本生化学会

研究キーワード 5

  • 蛍光測定

  • 数理解析

  • アミロイド線維

  • 等温滴定熱量計

  • 蛋白質間相互作用

研究分野 2

  • ライフサイエンス / 生物物理学 / 蛋白質凝集

  • ライフサイエンス / 構造生物化学 / 小胞体シャペロン

論文 20

  1. De novo design of a peptide ligand for specific affinity purification of human complement C1q

    Ryo Tsuchihashi, Misaki Kinoshita, Hiroaki Aino

    2026年4月1日

    出版者・発行元： openRxiv

    DOI： 10.64898/2026.03.30.714096 　

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    Abstract Affinity purification is a essential technique for isolating highly purified proteins; however, generating affinity ligands require significant time and financial investment. To address these limitations, this study proposes a novel affinity chromatography method utilizing in silico -designed cyclic peptides as ligands. Targeting Complement C1q (C1q), a plasma protein that plays crucial roles in classical complement pathway, we employed the biomolecular structure prediction model, AlphaFold2, to design specific binding cyclic peptides. Based on these designs, we synthesized lariat-type cyclic peptides characterized by disulfide cyclization and biotinylation, which were subsequently immobilized on streptavidin carriers. Performance tests confirmed that the resulting column specifically captured C1q, allowing for elution via a standard NaCl concentration gradient. Notably, high selectivity was preserved even in the presence of plasma, underscoring the ligand’s practical robustness. By overcoming traditional constraints through (1) rapid and simple design, (2) high specificity, and (3) universal versatility without genetic modification, this de novo design strategy represents a potential breakthrough in protein purification technologies. Highlights AI-driven de novo design generated a specific cyclic peptide ligand for Complement C1q The synthetic ligand enabled one-step purification of Complement C1q directly from human plasma Mild elution conditions preserved the target’s oligomeric structure and native interactome This label-free strategy offers a rapid, low-cost alternative to antibody-based chromatography

  2. Cyclic peptides space: The methodology of sequence selection to cover the comprehensive physical properties

    Ryo Tsuchihashi, Misaki Kinoshita

    2026年3月12日

    出版者・発行元： openRxiv

    DOI： 10.64898/2026.03.10.710724 　

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    Abstract Cyclic peptides have emerged as a pivotal modality for next-generation therapeutics, due to their superior biocompatibility, high selectivity, and structural stability. While AI-driven peptide design has advanced rapidly, conventional optimization algorithms are often constrained by initialization biases, which impede the efficient exploration of the vast chemical space. Here, we propose a novel methodology that integrates the protein language model ESM-2 with cyclic permutation averaging of embeddings to resolve this bottleneck. This approach establishes a comprehensive "peptide space", a high-dimensional vector representation that encapsulates the physicochemical and structural attributes of cyclic peptides. Our analysis reveals that random sequence selection results in a heterogeneous distribution within this space, potentially underrepresenting specific functional regions. Conversely, navigating this defined peptide space enables the selection of libraries that uniformly span diverse molecular properties. In a proof-of-concept study designing binders for β2-microglobulin (β2m), we demonstrate that initial sequences uniformly sampled from our peptide space yield superior candidates more efficiently than those derived from random selection. Furthermore, this framework facilitates the quantitative assessment of mutational perturbations on global peptide properties, supporting rational decision-making for both broad exploration and local optimization. This "peptide space" concept provides a foundational framework for defining appropriate search boundaries and enhancing computational efficiency in AI-mediated drug discovery. Graphic Abstract

  3. A unique leucine-valine adhesive motif supports structure and function of protein disulfide isomerase P5 via dimerization

    Masaki Okumura, Shingo Kanemura, Motonori Matsusaki, Misaki Kinoshita, Tomohide Saio, Dai Ito, Chihiro Hirayama, Hiroyuki Kumeta, Mai Watabe, Yuta Amagai, Young-Ho Lee, Shuji Akiyama, Kenji Inaba

    Structure　2021年4月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.str.2021.03.016 　

    ISSN：0969-2126

  4. Antipsychotic olanzapine-induced misfolding of proinsulin in the endoplasmic reticulum accounts for atypical development of diabetes. 国際誌

    Satoshi Ninagawa, Seiichiro Tada, Masaki Okumura, Kenta Inoguchi, Misaki Kinoshita, Shingo Kanemura, Koshi Imami, Hajime Umezawa, Tokiro Ishikawa, Robert B Mackin, Seiji Torii, Yasushi Ishihama, Kenji Inaba, Takayuki Anazawa, Takahiko Nagamine, Kazutoshi Mori

    eLife　9　2020年11月17日

    DOI： 10.7554/eLife.60970 　

    ISSN：2050-084X

  5. The protein disulfide isomerase family: from proteostasis to pathogenesis 査読有り

    Matsusaki, M, Kanemura, S, Kinoshita, M, Lee, Y.H, Inaba, K, Okumura, M

    Biochem. Biophys. Acta. General Subject　2020年1月

  6. Diverse Structural Conversion and Aggregation Pathways of Alzheimer's Amyloid-β (1-40). 査読有り

    Lin Y, Sahoo BR, Ozawa D, Kinoshita M, Kang J, Lim MH, Okumura M, Huh YH, Moon E, Jang JH, Lee HJ, Ryu KY, Ham S, Won HS, Ryu KS, Sugiki T, Bang JK, Hoe HS, Fujiwara T, Ramamoorthy A, Lee YH

    ACS nano　2019年7月

    DOI： 10.1021/acsnano.9b01578 　

    ISSN：1936-0851

  7. Dynamic assembly of protein disulfide isomerase in catalysis of oxidative folding

    Masaki Okumura, Kentaro Noi, Shingo Kanemura, Misaki Kinoshita, Tomohide Saio, Yuichi Inoue, Takaaki Hikima, Shuji Akiyama, Teru Ogura, Kenji Inaba

    Nature Chemical Biology　15　(5)　499-509　2019年5月

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1038/s41589-019-0268-8 　

    ISSN：1552-4450

    eISSN：1552-4469

  8. Zinc boosts EGCG's hIAPP amyloid Inhibition both in solution and membrane. 査読有り

    Lee YH, Lin Y, Cox SJ, Kinoshita M, Sahoo BR, Ivanova M, Ramamoorthy A

    Biochimica et biophysica acta. Proteins and proteomics　2018年11月

    DOI： 10.1016/j.bbapap.2018.11.006 　

    ISSN：1570-9639

  9. Graphene quantum dots prevent α-synucleinopathy in Parkinson's disease 査読有り

    Kim D, Yoo JM, Hwang H, Lee J, Lee SH, Yun SP, Park MJ, Lee M, Choi S, Kwon SH, Lee S, Kwon SH, Kim S, Park YJ, Kinoshita M, Lee YH, Shin S, Paik SR, Lee SJ, Lee S, Hong BH, Ko HS

    Nat. Nanotechnol.　2018年7月

    DOI： 10.1038/s41565-018-0179-y 　

    ISSN：1748-3387

  10. Energy landscape of polymorphic amyloid generation of β2-microglobulin revealed by calorimetry. 査読有り

    Kinoshita M, Lin Y, Dai I, Okumura M, Markova N, Ladbury JE, Sterpone F, Lee YH

    Chemical communications (Cambridge, England)　54　(57)　7995-7998　2018年7月

    DOI： 10.1039/c8cc02718h 　

    ISSN：1359-7345

  11. Impact of membrane curvature on amyloid aggregation. 査読有り

    Terakawa MS, Lin Y, Kinoshita M, Kanemura S, Itoh D, Sugiki T, Okumura M, Ramamoorthy A, Lee YH

    Biochimica et biophysica acta　2018年4月

    DOI： 10.1016/j.bbamem.2018.04.012 　

    ISSN：0006-3002

  12. Membrane-induced initial structure of α-synuclein control its amyloidogenesis on model membranes. 査読有り

    Terakawa MS, Lee YH, Kinoshita M, Lin Y, Sugiki T, Fukui N, Ikenoue T, Kawata Y, Goto Y

    Biochimica et biophysica acta. Biomembranes　1860　(3)　757-766　2018年3月1日

    出版者・発行元：

    DOI： 10.1016/j.bbamem.2017.12.011 　

    ISSN：1879-2642 0005-2736

  13. Kinetics and polymorphs of yeast prion Sup35NM amyloidogenesis 査読有り

    Misaki Kinoshita, Yuxi Lin, Masatoshi Nakatsuji, Takashi Inui, Young-Ho Lee

    INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES　102　1241-1249　2017年9月

    DOI： 10.1016/j.ijbiomac.2017.05.001 　

    ISSN：0141-8130

    eISSN：1879-0003

  14. Model membrane size-dependent amyloidogenesis of Alzheimer's amyloid-β peptides. 査読有り

    Kinoshita M, Kakimoto E, Terakawa MS, Lin Y, Ikenoue T, So M, Sugiki T, Ramamoorthy A, Goto Y, Lee YH

    Physical chemistry chemical physics : PCCP　19　(24)　16257-16266　2017年6月

    DOI： 10.1039/c6cp07774a 　

    ISSN：1463-9076

    eISSN：1463-9084

  15. Energetic basis on interactions between ferredoxin and ferredoxin NADP(+) reductase at varying physiological conditions 査読有り

    Misaki Kinoshita, Ju Yaen Kim, Satoshi Kume, Yuxi Lin, K. Hun Mok, Yosky Kataoka, Koichiro Ishimori, Natalia Markova, Genji Kurisu, Toshiharu Hase, Young-Ho Lee

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　482　(4)　909-915　2017年1月

    DOI： 10.1016/j.bbrc.2016.11.132 　

    ISSN：0006-291X

    eISSN：1090-2104

  16. Non-covalent forces tune the electron transfer complex between ferredoxin and sulfite reductase to optimize enzymatic activity 査読有り

    Ju Yaen Kim, Misaki Kinoshita, Satoshi Kume, G. T. Hanke, Toshihiko Sugiki, John E. Ladbury, Chojiro Kojima, Takahisa Ikegami, Genji Kurisu, Yuji Goto, Toshiharu Hase, Young-Ho Lee

    BIOCHEMICAL JOURNAL　473　(21)　3837-3854　2016年11月

    DOI： 10.1042/BCJ20160658 　

    ISSN：0264-6021

    eISSN：1470-8728

  17. A thiirane linker for isopeptide mimetics by peptide ligation 査読有り

    Toru Kawakami, Yuichi Mishima, Misaki Kinoshita, Young-Ho Lee, Isao Suetake

    TETRAHEDRON LETTERS　57　(19)　2112-2115　2016年5月

    DOI： 10.1016/j.tetlet.2016.04.006 　

    ISSN：0040-4039

  18. Amorphous Aggregation of Cytochrome c with Inherently Low Amyloidogenicity Is Characterized by the Metastability of Supersaturation and the Phase Diagram 査読有り

    Yuxi Lin, Jozsef Kardos, Mizue Imai, Tatsuya Ikenoue, Misaki Kinoshita, Toshihiko Sugiki, Koichiro Ishimori, Yuji Goto, Young-Ho Lee

    LANGMUIR　32　(8)　2010-2022　2016年3月

    DOI： 10.1021/acs.langmuir.5b03810 　

    ISSN：0743-7463

  19. Physicochemical natures of interfaces control activity of ferredoxin NADP+ reductase through its interprotein interactions with ferredoxin 査読有り

    Misaki Kinoshita, Ju yaen Kim, Satoshi Kume, Yukiko Sakakibara, Toshihiko Sugiki, Chojiro Kojima, Genji Kurisu, Takahisa Ikegami, Toshiharu Hase, Yoko Kimata-Ariga, Young-Ho Lee

    BBA - Bioenergetics　1847　(10)　1200-1211　2015年10月

    出版者・発行元： ELSEVIER

    DOI： 10.1016/j.bbabio.2015.05.023 　

    ISSN：0005-2728

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    フェレドキシン依存NADP+還元酵素とフェレドキシンとの物理化学的な相互作用解析

  20. Physicochemical nature of interfaces controlling ferredoxin NADP(+) reductase activity through its interprotein interactions with ferredoxin. 国際誌 査読有り

    Kinoshita M, Kim JY, Kume S, Sakakibara Y, Sugiki T, Kojima C, Kurisu G, Ikegami T, Hase T, Kimata-Ariga Y, Lee YH

    Biochimica et biophysica acta　1847　(10)　1200-1211　2015年10月

    DOI： 10.1016/j.bbabio.2015.05.023 　

    ISSN：0006-3002

︎全件表示 ︎最初の5件までを表示

MISC 9

  1. Impact of membrane curvature on amyloid aggregation 査読有り

    Mayu S. Terakawa, Yuxi Lin, Misaki Kinoshita, Shingo Kanemura, Dai Itoh, Toshihiko Sugiki, Masaki Okumura, Ayyalusamy Ramamoorthy, Young-Ho Lee

    Biochimica et Biophysica Acta - Biomembranes　2018年

    出版者・発行元： Elsevier B.V.

    DOI： 10.1016/j.bbamem.2018.04.012 　

    ISSN： 1879-2642 0005-2736

  2. Biochemical and biophysical methods to examine the effects of site-directed mutagenesis on enzymatic activities and interprotein interactions 査読有り

    Misaki Kinoshita, Ju Yaen Kim, Yuxi Lin, Natalia Markova, Toshiharu Hase, Young-Ho Lee

    Methods in Molecular Biology　1498　439-460　2017年

    出版者・発行元： Humana Press Inc.

    DOI： 10.1007/978-1-4939-6472-7_30 　

    ISSN： 1064-3745

  3. Thermodynamics of protein-protein interactions examined by isothermal titration calorimetery 招待有り 査読有り

    Kim JY, Kinoshita M, Lin Y, Lee YH

    Biochemistry Research Trends, Protein-Protein interactions　67-80　2017年

  4. Molecular structure of amyloid fibrils revealed by thermodynamics 招待有り 査読有り

    Ikenoue T, Lin Y, Kinoshita M, Sakurai K, Goto Y, Lee YH

    Biochemistry Research Trends, Protein-Protein interactions　81-96　2017年

  5. Practical tips for MicroCal PEAQ-ITC experiments: troubleshooting and additional help to maximize performance 招待有り 査読有り

    Kinoshita M, Kim JY, Lin Y, Lee YH

    Malvern Technical note, Malvern Instrument Ltd.　2017年

  6. Biophysical application of calorimetric methods to protein misfolding and aggregation examinations 招待有り 査読有り

    Ikenoue T, Kinoshita M, Lin Y, Lee YH

    White paper (Malvern Instrument Ltd.)　2017年

  7. チイランリンカーを用いるイソペプチド類似構造を介したヒストンペプチドのユビキチン化

    川上徹, 三島優一, 木下岬, 李映昊, 末武勲, 末武勲

    日本生化学会大会(Web)　89th　2016年

  8. チイランリンカーを用いることによりイソペプチド摸倣体を経由してヒストンペプチドのユビキチン化

    KAWAKAMI Toru, MISHIMA Yuichi, KINOSHITA Misaki, LEE Young-Ho, SUETAKE Isao, SUETAKE Isao

    Peptide Science　2016　2016年

    ISSN： 1344-7661

  9. Delicate Balance of Noncovalent Forces Control the Electron Transfer Complex between Ferredoxin and Sulfite Reductase to Optimize Enzymatic Activity

    Juyaen Kim, Misaki Kinoshita, Takahisa Ikegami, Genji Kurisu, Yuji Goto, Toshiharu Hase, Young-Ho Lee

    PROTEIN SCIENCE　24　64-65　2015年10月

    ISSN： 0961-8368

    eISSN： 1469-896X

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講演・口頭発表等 1

  1. Physicochemical nature of interfaces controlling ferredoxin NADP+ reductase activity through its interprotein interactions with frredoxin 国際会議

    Kinoshita M, Kim JY, Sugiki T, Kojima C, KUrisu G, Ikegami T, Ariga YK, Hase T, Lee YH

    International Conference on Magnetic Resonance in Biological Systems　2016年