Details of the Researcher

PHOTO

Shingo Kanemura
Section
Frontier Research Institute for Interdisciplinary Sciences
Job title
Assistant Professor
Degree

  • 博士（生命科学）（東北大学）

  • 修士（理学）（関西学院大学）

e-Rad No.
50803178
Profile

生命はタンパク質によって維持されています。ヒトゲノムに含まれるタンパク質をコードする遺伝子は現在までに約2万個同定されており、これら遺伝子から10万種以上のタンパク質が翻訳されると考えられています。そのうち約40％が膜タンパク質または分泌タンパク質であると予測されており、そのほとんどは少なくとも1つのジスルフィド結合を有していることがわかっています。ジスルフィド結合は、タンパク質中の2つのシステイン残基のチオール基間の共有結合です。タンパク質の立体構造安定性に重要な役割を果たすジスルフィド結合の形成は、主に細胞小器官の一つ小胞体で起こります。細胞外環境においてもジスルフィド結合の形成や切断(レドックス反応)が起こっており、活性、リガンド親和性、局在化、多量体化などのタンパク質機能の変化を媒介することはわかっていますが、細胞内レドックスに比べて細胞外レドックスの理解はまだまだできていません。

私はこれまでに小胞体内(細胞内)におけるレドックスネットワークの一端を明らかにしてきました。今後は細胞外レドックスの理解へと研究範囲を拡張していきます。現在では、細胞外レドックスと生体防御システムとの関連に着目した研究を展開しており、生化学、構造生物学、細胞生物学、ウイルス学、計算科学、有機化学、薬学分野などを融合した学際研究により「細胞外レドックスを介した生体防御システムの理解」を目指しています。

Research History 4

  • 2024/04 - Present
    Tohoku University　FRIS　Assistant Professor

  • 2018/04 - 2024/03
    Kwansei Gakuin University　School of Science

  • 2017/04 - 2018/03
    Tohoku University　Frontier Research Institute for Interdisciplinary Sciences

  • 2015/04 - 2017/03
    日本学術振興会

Education 3

  • Tohoku University　Graduate School, Division of Life Science

    2014/04 - 2017/03

  • Kwansei Gakuin University　Graduate School, Division of Science and Engineering

    2012/04 - 2014/03

  • Kwansei Gakuin University　Faculty of Science and Engineering

    2007/04 - 2012/03

Committee Memberships 4

  • 実行委員、2025 Joint Conference - Korean Society for Protein Science & Protein Science Society of Japan

    2025 -

  • 実行委員、2024 Joint Conference - Korean Society for Protein Science & Protein Science Society of Japan

    2024 -

  • 実行委員、The Crystallographic Society of Japan 2022 (CrSJ2022）(2022年度日本結晶学会年会)

    2022 -

  • 実行委員、The 6th International Symposium on Diffraction Structural Biology (ISDSB2019）(第６回回折構造生物国際シンポジウム)

    2019 -

Professional Memberships 4

  • 日本結晶学会

    2022/04 - Present

  • 日本生化学会

  • 日本分子生物学会

  • 日本蛋白質科学会

Research Interests 6

  • レドックス

  • ジスルフィド結合

  • ウイルス

  • Structural Biology

  • Biochemistry

  • Protein Science

Research Areas 2

  • Life sciences / Biophysics /

  • Life sciences / Structural biochemistry /

Awards 3

  1. 若手奨励賞

    2023/07　日本蛋白質科学会

  2. 生命科学研究科長賞

    2017/03　東北大学大学院

  3. 生命科学会会長賞

    2017/02　東北大学大学院

Papers 22

  1. Ca2+-triggered allosteric catalysts crosstalk with cellular redox systems through their foldase- and reductase-like activities

    Rumi Mikami, Yuhei Sato, Shingo Kanemura, Takahiro Muraoka, Masaki Okumura, Kenta Arai

    Communications Chemistry　2025/03/11

    DOI： 10.1038/s42004-025-01466-6 　

  2. ER Oxidoreductin 1‐Like Activity of Cyclic Diselenides Drives Protein Disulfide Isomerase in an Electron Relay System International-journal Peer-reviewed

    Rumi Mikami, Yuya Nishizawa, Yuki Iwata, Shingo Kanemura, Masaki Okumura, Kenta Arai

    ChemBioChem　e202400739　2024/11/23

    Publisher: Wiley

    DOI： 10.1002/cbic.202400739 　

    ISSN： 1439-4227

    eISSN： 1439-7633

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    Abstract Disulfide formation generally involves a two‐electron oxidation reaction between cysteine residues. Additionally, disulfide formation is an essential post‐translational modification for the structural maturation of proteins. This oxidative folding is precisely controlled by an electron relay network constructed by protein disulfide isomerase (PDI), with a CGHC sequence as the redox‐active site, and its family enzymes. Creating reagents that mimic the functions of these enzymes facilitates folding during chemical protein synthesis. In this study, we aimed to imitate a biological electron relay system using cyclic diselenide compounds as surrogates for endoplasmic reticulum oxidoreductin 1 (Ero1), which is responsible for the re‐oxidation of PDI. Oxidized PDI (PDIox) introduces disulfide bonds into substrate proteins, resulting in its conversion to reduced PDI (PDIred). The PDIred is then re‐oxidized to PDIox by a coexisting cyclic diselenide compound, thereby restoring the function of PDI as a disulfide‐forming agent. The produced diselenol state is readily oxidized to the original diselenide state with molecular oxygen, continuously sustaining the PDI catalytic cycle. This artificial electron relay system regulating enzymatic PDI function effectively promotes the oxidative folding of disulfide‐containing proteins, such as insulin – a hypoglycemic formulation – by enhancing both yield and reaction velocity.

  3. Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions International-journal Peer-reviewed

    Koki Suzuki, Ryoya Nojiri, Motonori Matsusaki, Takuya Mabuchi, Shingo Kanemura, Kotone Ishii, Hiroyuki Kumeta, Masaki Okumura, Tomohide Saio, Takahiro Muraoka

    Chemical Science　15　(32)　12676-12685　2024/07/29

    DOI： 10.1039/d4sc02123a 　

    ISSN： 2041-6520

    eISSN： 2041-6539

  4. Boosting the enzymatic activity of CxxC motif-containing PDI family members. International-journal Peer-reviewed

    Tsubura Kuramochi, Yukino Yamashita, Kenta Arai, Shingo Kanemura, Takahiro Muraoka, Masaki Okumura

    Chemical communications (Cambridge, England)　60　(48)　6134-6137　2024/06/11

    DOI： 10.1039/d4cc01712a 　

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    Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of members of the protein disulphide isomerase (PDI) family and thus can be used to accelerate folding processes and increase the production of native proteins by minimal loading in comparison to glutathione.

  5. Semi-enzymatic acceleration of oxidative protein folding by N-methylated heteroaromatic thiols International-journal Peer-reviewed

    Shunsuke Okada, Yosuke Matsumoto, Rikana Takahashi, Kenta Arai, Shingo Kanemura, Masaki Okumura, Takahiro Muraoka

    Chemical Science　14　(28)　7630-7636　2023/06

    Publisher: Royal Society of Chemistry (RSC)

    DOI： 10.1039/d3sc01540h 　

    ISSN： 2041-6520

    eISSN： 2041-6539

  6. A unique leucine-valine adhesive motif supports structure and function of protein disulfide isomerase P5 via dimerization International-journal International-coauthorship Peer-reviewed

    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　29　(12)　1357-1370.e6　2021/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.str.2021.03.016 　

    ISSN： 0969-2126

  7. Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding International-journal International-coauthorship Invited Peer-reviewed

    Motonori Matsusaki, Rina Okada, Yuya Tanikawa, Shingo Kanemura, Dai Ito, Yuxi Lin, Mai Watabe, Hiroshi Yamaguchi, Tomohide Saio, Young-Ho Lee, Kenji Inaba, Masaki Okumura

    Biology　10　(11)　1112-1112　2021/10/28

    Publisher: MDPI AG

    DOI： 10.3390/biology10111112 　

    eISSN： 2079-7737

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    P5 is one of protein disulfide isomerase family proteins (PDIs) involved in endoplasmic reticulum (ER) protein quality control that assists oxidative folding, inhibits protein aggregation, and regulates the unfolded protein response. P5 reportedly interacts with other PDIs via intermolecular disulfide bonds in cultured cells, but it remains unclear whether complex formation between P5 and other PDIs is involved in regulating enzymatic and chaperone functions. Herein, we established the far-western blot method to detect non-covalent interactions between P5 and other PDIs and found that PDI and ERp72 are partner proteins of P5. The enzymatic activity of P5-mediated oxidative folding is up-regulated by PDI, while the chaperone activity of P5 is stimulated by ERp72. These findings shed light on the mechanism by which the complex formations among PDIs drive to synergistically accelerate protein folding and prevents aggregation. This knowledge has implications for understanding misfolding-related pathology.

  8. Ca2+ regulates ERp57-calnexin complex formation International-journal International-coauthorship Peer-reviewed

    Tanikawa Y, Kanemura S, Ito D, Lin Y, Matsusaki M, Kuroki K, Yamaguchi H, Maenaka K, Lee Y. -H, Inaba K, Okumura M

    Molecules　26　(10)　2853-2853　2021/05

    Publisher: MDPI AG

    DOI： 10.3390/molecules26102853 　

    eISSN： 1420-3049

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    ERp57, a member of the protein disulfide isomerase family, is a ubiquitous disulfide catalyst that functions in the oxidative folding of various clients in the mammalian endoplasmic reticulum (ER). In concert with ER lectin-like chaperones calnexin and calreticulin (CNX/CRT), ERp57 functions in virtually all folding stages from co-translation to post-translation, and thus plays a critical role in maintaining protein homeostasis, with direct implication for pathology. Here, we present mechanisms by which Ca2+ regulates the formation of the ERp57-calnexin complex. Biochemical and isothermal titration calorimetry analyses revealed that ERp57 strongly interacts with CNX via a non-covalent bond in the absence of Ca2+. The ERp57-CNX complex not only promoted the oxidative folding of human leukocyte antigen heavy chains, but also inhibited client aggregation. These results suggest that this complex performs both enzymatic and chaperoning functions under abnormal physiological conditions, such as Ca2+ depletion, to effectively guide proper oxidative protein folding. The findings shed light on the molecular mechanisms underpinning crosstalk between the chaperone network and Ca2+.

  9. PDI Family Members as Guides for Client Folding and Assembly International-journal Invited Peer-reviewed

    Shingo Kanemura, Motonori Matsusaki, Kenji Inaba, Masaki Okumura

    International Journal of Molecular Sciences　21　(24)　9351-9351　2020/12/08

    Publisher: MDPI AG

    DOI： 10.3390/ijms21249351 　

    eISSN： 1422-0067

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    Complicated and sophisticated protein homeostasis (proteostasis) networks in the endoplasmic reticulum (ER), comprising disulfide catalysts, molecular chaperones, and their regulators, help to maintain cell viability. Newly synthesized proteins inserted into the ER need to fold and assemble into unique native structures to fulfill their physiological functions, and this is assisted by protein disulfide isomerase (PDI) family. Herein, we focus on recent advances in understanding the detailed mechanisms of PDI family members as guides for client folding and assembly to ensure the efficient production of secretory proteins.

  10. Antipsychotic olanzapine-induced misfolding of proinsulin in the endoplasmic reticulum accounts for atypical development of diabetes International-journal International-coauthorship Peer-reviewed

    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　2020/11/17

    Publisher: eLife Sciences Publications, Ltd

    DOI： 10.7554/elife.60970 　

    eISSN： 2050-084X

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    Second-generation antipsychotics are widely used to medicate patients with schizophrenia, but may cause metabolic side effects such as diabetes, which has been considered to result from obesity-associated insulin resistance. Olanzapine is particularly well known for this effect. However, clinical studies have suggested that olanzapine-induced hyperglycemia in certain patients cannot be explained by such a generalized mechanism. Here, we focused on the effects of olanzapine on insulin biosynthesis and secretion by mouse insulinoma MIN6 cells. Olanzapine reduced maturation of proinsulin, and thereby inhibited secretion of insulin; and specifically shifted the primary localization of proinsulin from insulin granules to the endoplasmic reticulum. This was due to olanzapine’s impairment of proper disulfide bond formation in proinsulin, although direct targets of olanzapine remain undetermined. Olanzapine-induced proinsulin misfolding and subsequent decrease also occurred at the mouse level. This mechanism of olanzapine-induced β-cell dysfunction should be considered, together with weight gain, when patients are administered olanzapine.

  11. Characterization of the endoplasmic reticulum–resident peroxidases GPx7 and GPx8 shows the higher oxidative activity of GPx7 and its linkage to oxidative protein folding International-journal International-coauthorship Peer-reviewed

    Shingo Kanemura, Elza Firdiani Sofia, Naoya Hirai, Masaki Okumura, Hiroshi Kadokura, Kenji Inaba

    Journal of Biological Chemistry　295　(36)　12772-12785　2020/09

    Publisher: Elsevier BV

    DOI： 10.1074/jbc.ra120.013607 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  12. Protein secondary structure determines the temporal relationship between folding and disulfide formation International-journal International-coauthorship Peer-reviewed

    Philip J. Robinson, Shingo Kanemura, Xiaofei Cao, Neil J. Bulleid

    Journal of Biological Chemistry　295　(8)　2438-2448　2020/02

    Publisher: Elsevier BV

    DOI： 10.1074/jbc.ra119.011983 　

    ISSN： 0021-9258

  13. Dynamic assembly of protein disulfide isomerase in catalysis of oxidative folding International-journal Peer-reviewed

    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　2019/05/01

    Publisher: Nature Publishing Group

    DOI： 10.1038/s41589-019-0268-8 　

    ISSN： 1552-4469 1552-4450

  14. The Protein Disulfide Isomerase Family: from proteostasis to pathogenesis. Peer-reviewed

    Matsusaki M, Kanemura S, Kinoshita M, Lee YH, Inaba K, Okumura M

    Biochimica et biophysica acta. General subjects　2019/04

    DOI： 10.1016/j.bbagen.2019.04.003 　

  15. Ero1-mediated reoxidation of protein disulfide isomerase accelerates the folding of cone snail toxins International-journal International-coauthorship Peer-reviewed

    Henrik O’brien, Shingo Kanemura, Masaki Okumura, Robert P. Baskin, Pradip K. Bandyopadhyay, Baldomero M. Olivera, Lars Ellgaard, Kenji Inaba, Helena Safavi-Hemami

    International Journal of Molecular Sciences　19　(11)　2018/11/01

    Publisher: MDPI AG

    DOI： 10.3390/ijms19113418 　

    ISSN： 1422-0067 1661-6596

  16. Impact of membrane curvature on amyloid aggregation Peer-reviewed

    Terakawa M. S., Lin Y., Kinoshita M., Kanemura S., Itoh D., Sugiki T., Okumura M., Ramamoorthy A. and Lee Y. H.

    Biochimica et Biophysica Acta - Biomembranes　2018

    Publisher: Elsevier B.V.

    DOI： 10.1016/j.bbamem.2018.04.012 　

    ISSN： 1879-2642 0005-2736

  17. Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface Peer-reviewed

    Watanabe S., Harayama M., Kanemura S., Sitia R. and Inaba K.

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　114　(16)　E3224-E3232　2017/04

    DOI： 10.1073/pnas.1621426114 　

    ISSN： 0027-8424

  18. Human ER Oxidoreductin-1 alpha (Ero1 alpha) Undergoes Dual Regulation through Complementary Redox Interactions with Protein-Disulfide Isomerase Peer-reviewed

    Kanemura S., Okumura M., Yutani K., Ramming T., Hikima T., Appenzeller-Herzog C., Akiyama S. and Inaba K.

    JOURNAL OF BIOLOGICAL CHEMISTRY　291　(46)　23952-23964　2016/11

    DOI： 10.1074/jbc.M116.735662 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  19. Cysteines 208 and 241 in Ero1 alpha are required for maximal catalytic turnover Peer-reviewed

    Ramming T.#, Kanemura S.#, Okumura M., Inaba K. and Appenzeller-Herzog C. (#These authors contributed equally to this work.)

    REDOX BIOLOGY　7　14-20　2016/04

    DOI： 10.1016/j.redox.2015.11.004 　

    ISSN： 2213-2317

  20. A PDI-catalyzed thiol-disulfide switch regulates the production of hydrogen peroxide by human Ero1 Peer-reviewed

    Ramming T., Okumura M., Kanemura S., Baday S., Birk J., Moes S., Spiess M., Jenö P., Bernèche S., Inaba K. and Appenzeller-Herzog C.

    FREE RADICAL BIOLOGY AND MEDICINE　83　361-372　2015/06

    DOI： 10.1016/j.freeradbiomed.2015.02.011 　

    ISSN： 0891-5849

    eISSN： 1873-4596

  21. Inhibition of the Functional Interplay between Endoplasmic Reticulum (ER) Oxidoreduclin-1 alpha (Ero1 alpha) and Protein-disulfide Isomerase (PDI) by the Endocrine Disruptor Bisphenol A Peer-reviewed

    Okumura M., Kadokura H., Hashimoto S., Yutani K., Kanemura S., Hikima T., Hidaka Y., Ito L., Shiba K., Masui S., Imai D., Imaoka K., Yamaguchi H. and Inaba K.

    JOURNAL OF BIOLOGICAL CHEMISTRY　289　(39)　27004-27018　2014/09

    DOI： 10.1074/jbc.M114.564104 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  22. Radically Different Thioredoxin Domain Arrangement of ERp46, an Efficient Disulfide Bond Introducer of the Mammalian PDI Family Peer-reviewed

    Kojima R.#, Okumura M.#, Masui S., Kanemura S., Inoue M., Saiki M., Yamaguchi H., Hikima T., Suzuki M., Akiyama S. and Inaba K. (#These authors contributed equally to this work.)

    STRUCTURE　22　(3)　431-443　2014/03

    DOI： 10.1016/j.str.2013.12.013 　

    ISSN： 0969-2126

    eISSN： 1878-4186

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Misc. 15

  1. Ca2+-driven PDIA6 phase separation to ensure proinsulin quality control International-journal International-coauthorship

    Young-Ho Lee, Tomohide Saio, Mai Watabe, Motonori Matsusaki, Shingo Kanemura, Yuxi Lin, Taro Mannen, Tsubura Kuramochi, Katsuya Iuchi, Michiko Tajiri, Kotono Suzuki, Yan Li, Yunseok Heo, Yuka Kamada, Kenta Arai, Mayuko Hashimoto, Satoshi Ninagawa, Yoshikazu Hattori, Hiroyuki Kumeta, Airu Takeuchi, Hiroya Abe, Eiichiro Mori, Takahiro Muraoka, Tsukasa Okiyoneda, Satoko Akashi, Michele Vendruscolo, Kenji Inaba, Masaki Okumura

    2024/07/30

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2024.07.30.605722 　

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    Abstract The endoplasmic reticulum (ER) plays key roles in protein quality control1,2and dynamic Ca2+storage3,4in eukaryotic cells. However, the protein homeostasis (proteostasis) system that regulates these ER functions is still incompletely characterised. Previous study revealed the importance of oligomerization in the function PDIA1, an ER-resident disulfide isomerase and molecular chaperone, regulates oligomeric states in accordance with client folding5. This result suggests that at least some of the 20 members of other PDI family may undergo regulated self-assembly in order to optimally function. Here, we show that Ca2+triggers the phase separation of PDIA6 into liquid-like condensates. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the Ca2+-driven condensation of PDIA6 recruits PDIA3 and proinsulin, thus increasing their local concentrations. This process results in the 30-fold enhancement of proinsulin folding and in the inhibition of proinsulin aggregation. Our findings shed light on a condensation-driven Ca2+-mediated proteostasis cascade in the ER by revealing how the efficiency of the protein folding process can be enhanced within quality control granules.

  2. Conserved loop of a phase modifier endows protein condensates with fluidity International-journal

    Honoka Kawamukai, Motonori Matsusaki, Takanari Tanimoto, Mai Watabe, Ken Morishima, Shunsuke Tomita, Yoichi Shinkai, Tatsuya Niwa, Taro Mannen, Hiroyuki Kumeta, Hitoki Nanaura, Kotona Kato, Takuya Mabuchi, Yuichiro Aiba, Takeru Uehara, Noriyoshi Isozumi, Yoshika Hara, Shingo Kanemura, Hiroyoshi Matsumura, Kazuma Sugie, Koichiro Ishimori, Takahiro Muraoka, Masaaki Sugiyama, Masaki Okumura, Eiichiro Mori, Takuya Yoshizawa, Tomohide Saio

    2024/07/04

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2024.07.03.601791 　

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    Abstract Dipeptide repeats (DPRs) that are gene products from abnormal hexanucleotide repeat expansion inC9orf72trigger amyotrophic lateral sclerosis (ALS) through unknown mechanism. This study highlights, importin Karyopherinβ2 (Kapβ2), which is responsible for nuclear transport and phase modification of RNA-binding proteins (RBPs), as a major DPR target. We demonstrate DPR accumulation in the nucleus via Kapβ2-mediated transport, which results in dose-dependent toxicity observed in nematode and yeast models. In vitro interaction studies exploiting chemical probe arrays and biophysical measurements reveal multivalent DPR binding to Kapβ2, including at the conserved acidic loop. Refractive index and fluorescence imaging coupled with biochemical assays unveiled that binding of excess DPRs to the acidic loop turns a phase modifier Kapβ2 into phase disrupter, resulting more condensed and viscous RBP condensates. Our findings provides molecular insight intoC9orf72-ALS related to age and repeat expansion.

  3. Client recognition differences between PDI and ERp46 to guide oxidative folding International-journal International-coauthorship

    Tomohide Saio, Kotone Ishii, Motonori Matsusaki, Hiroyuki Kumeta, Shingo Kanemura, Masaki Okumura

    2024/03/08

    DOI： 10.1101/2024.03.04.583432 　

  4. 生物学的相分離の多元的理解～屈折率表示を例に～ International-coauthorship Invited

    渡部マイ, 金村進吾, 李映昊, 奥村正樹

    月刊細胞 特集「LC（Low-Complexity）ドメインの生物学」　2024/01

  5. Zinc finger domains bind low-complexity domain polymers International-journal

    Naohiko Iguchi, Noriyoshi Isozumi, Yoshikazu Hattori, Tomohiro Imamura, Masatomo So, Hitoki Nanaura, Takao Kiriyama, Nobuyuki Eura, Minako Yamaoka, Mari Nakanishi, Masashi Mori, Shinya Ohki, Hiroyuki Kumeta, Hironori Koga, Mai Watabe, Takuya Mabuchi, Shingo Kanemura, Masaki Okumura, Takuya Yoshizawa, Ichiro Ota, Naoki Suzuki, Masashi Aoki, Yoshito Yamashiro, Tomohide Saio, Kazuma Sugie, Eiichiro Mori

    bioRxiv　2023/10/29

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2023.10.29.564599 　

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    Self-association of low-complexity protein sequences (LC domains) is important for polymer formation. Several molecular chaperones are involved in the regulation of LC domain polymer formation. However, the mechanisms underlying cell recognition of LC domain polymers remain unclear. Here we show that zinc finger domains (ZnFs) bind LC domains of RNA-binding proteins in a cross-β polymer-dependent manner. ZnFs bound to LC domain hydrogels and suppressed LC domain polymer formation. Moreover, ZnFs preferentially recognize LC domains in the polymeric state. These findings suggest that ZnFs act as physiological regulators of LC domain polymer formation.

  6. Dose-response relationship for the resistance of human insulin to degradation by insulin-degrading enzyme International-journal International-coauthorship

    Masaki Okumura, Tsubura Kuramochi, Yuxi Lin, Ran Furukawa, Kenji Mizutani, Takeshi Yokoyama, Mingeun Kim, Mi Hee Lim, Hyon-Seung Yi, Kenta Arai, Hiroshi Yamaguchi, Hironobu Hojo, Michio Iwaoka, Yoshikazu Tanaka, Sam-Yong Park, Kenji Inaba, Shingo Kanemura, Young-Ho Lee

    bioRxiv　2023/04

    DOI： 10.1101/2023.04.08.536135 　

  7. Elucidating the Peptide Degradation Mechanism by Insulin Degrading Enzyme International-coauthorship

    Tsubura Kuramochi, Shingo Kanemura, Ran Furukawa, Hiroshi Yamaguchi, Kenta Arai, Young-Ho Lee, Masaki Okumura

    Peptide Science 2022　2023/03

  8. 小胞体ジスルフィド結合形成ネットワークを支える酵素群の構造基盤 Invited

    金村進吾, 稲葉謙次, 奥村正樹

    結晶学会誌　64　209-210　2022

  9. 小胞体内におけるMHCの品質管理 Invited

    金村進吾, 松崎元紀, 前仲勝実, 稲葉謙次, 奥村正樹

    月刊「臨床免疫・アレルギー科」　74　(5)　419-426　2020/11

    Publisher: (有)科学評論社

    ISSN： 1881-1930

  10. STRUCTURAL ANALYSES OF AN N-TERMINAL EXTRACELLULAR DOMAIN OF THE AMYLOID PRECURSOR PROTEIN Peer-reviewed

    2018　23-23　2019/03

    ISSN： 1344-7661

  11. Structural Analyses of a Linker Region of the Amyloid Precursor Protein Peer-reviewed

    Mizuho Imamura, Shingo Kanemura, Masaki Okumura, Hiroshi Yamaguchi, Shigeru Shimamoto, Yuji Hidaka

    Peptide Science　2017　206-207　2018/03

    ISSN： 1344-7661

  12. Structural Analyses of a Linker Region of the Amyloid Precursor Protein International-journal

    Mizuho Imamura, Shingo Kanemura, Masaki Okumura, Shigeru Shimamoto, Yuji Hidaka

    BIOPHYSICAL JOURNAL　114　(3)　78A-78A　2018/02

    ISSN： 0006-3495

    eISSN： 1542-0086

  13. X線小角散乱解析が明らかにしたPDIファミリータンパク質ERp46及びPDI酸化酵素Ero1αの構造ダイナミクスと機能 Invited

    金村進吾, 奥村正樹, 稲葉謙次

    分子研レターズ　2017

  14. 新規PDIファミリータンパク質ERp46の構造と機能 Invited

    奥村正樹, 金村進吾, 稲葉謙次

    生物物理　2015

  15. A pH-dependent conformational change in a soluble extracellular domain of amyloid precursor protein Peer-reviewed

    Kanemura S., Okumura M., Yutani K., Hikima T., Niinobe M., Yamaguchi H. and Hidaka Y.

    Peptide Science　2013

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Presentations 36

  1. 細胞外レドックス酵素によるウイルス失活化機構の解明 International-coauthorship

    金村進吾, 橋本里菜, 松崎元紀, 馬渕拓哉, 渡部マイ, 齋尾智英, 高山和雄, 李映昊, 奥村正樹

    第7回遅延制御超分子化学研究会　2024/12/01

  2. 人工PDIの創製

    野澤魁清, 金村進吾, 山口宏, 村岡貴博, 奥村正樹

    第7回遅延制御超分子化学研究会　2024/12/01

  3. PDIファミリー酵素ERp57による基質の酸化的フォールディング触媒機構の解明

    山本菜月, 石井琴音, 武内愛留, 松﨑元紀, 山口宏, 金村進吾, 奥村正樹

    第7回遅延制御超分子化学研究会　2024/12/01

  4. 小胞体局在シャペロン群による SOD1の機能制御機構の解明

    住本龍哉, 金村進吾, 山口宏, 中林孝和, 奥村正樹

    第7回遅延制御超分子化学研究会　2024/12/01

  5. PDIファミリー酵素ERp57を中心とした酸化的フォールディング触媒の解明

    武内愛留, 渡部マイ, 金村進吾, 奥村正樹

    第7回遅延制御超分子化学研究会　2024/12/01

  6. PDIファミリーによる酸化的フォールディング触媒機構の解明

    石井琴音, 金村進吾, 久米田博之, 松﨑元紀, 富田峻介, 林雨曦, 李映昊, 齋尾智英, 奥村正樹

    第7回遅延制御超分子化学研究会　2024/12/01

  7. タンパク質品質管理顆粒からストレス顆粒への液固相転移メカニズムの理解

    渡部マイ, 金村進吾, 鈴木琴乃, 坂和範, 佐藤伸一, 松﨑元紀, 稲葉謙次, 中林孝和, 李映昊, 齋尾智英, 奥村正樹

    第7回遅延制御超分子化学研究会　2024/12/01

  8. 小胞体局在酵素ERp57を中心としたタンパク質品質管理機構の解明

    武内愛留, 松﨑元紀, 齋尾智英, 稲葉謙次, 金村進吾, 奥村正樹

    第47回日本分子生物学会年会　2024/11/28

  9. フォールディングを触媒するPDIとERp46のクライアントタンパク質認識機構の理解

    石井琴音, 金村進吾, 久米田博之, 松﨑元紀, 富田峻介, 林雨曦, 李映昊, 齋尾智英, 奥村正樹

    第47回日本分子生物学会年会　2024/11/28

  10. タンパク質品質管理顆粒からストレス顆粒への液固相転移メカニズムの理解

    渡部マイ, 金村進吾, 鈴木琴乃, 坂和範, 佐藤伸一, 松﨑元紀, 稲葉謙次, 中林孝和, 李映昊, 齋尾智英, 奥村正樹

    第47回日本分子生物学会年会　2024/11/28

  11. 沖縄型神経原性筋萎縮症（HMSN-P）患者の株化細胞における網羅的遺伝子発現解析

    五十嵐ありさ, 諏訪園秀吾, 青木大芽, 飯田貴也, 小林奈々, 阿部幸美, 藤井陽子, スルタナサラ, 榎本友美, 山毛利雅彦, 柳久美子, 松原洋一, 金村進吾, 奥村正樹, 筒井正人, 要匡

    第47回日本分子生物学会年会　2024/11/26

  12. Development of a novel modality for redox catalysis-based drug discovery to combat viral infections International-presentation Invited

    Kanemura S., Okumura M.

    MASP-Taiwan　2024/11/20

  13. Ca2+をトリガースイッチとする酸化還元酵素様アロステリック触媒の開発

    三神瑠美, 金村進吾, 奥村正樹, 荒井堅太

    第97回生化学会　2024/11/06

  14. 酸化還元酵素によるウイルス失活化の分子機構解明 International-coauthorship

    金村進吾, 橋本里菜, 松崎元紀, 馬渕拓哉, 渡部マイ, 齋尾智英, 高山和雄, 李映昊, 奥村正樹

    学際高等研究教育院・学際科学フロンティア研究所共催 全領域合同研究交流会　2024/11/05

  15. Understanding the mechanism of viral inactivation by extracellular redox enzymes International-presentation International-coauthorship

    Kanemura S., Hashimoto R., Matsusaki M., Mabuchi T., Watabe M., Saio T., Takayama K., Lee Y -H., Okumura M.

    2024/10/22

  16. Chemical booster of the enzymatic PDI family activity via redox active site International-presentation

    Kuramochi T., Yamashita Y., Arai K., Kanemura S., Muraoka T., Okumura M.

    EMBO Workshop-The endoplasmic reticulum – Guardian of cellular homeostasis　2024/10/22

  17. Elucidating the enzymatic reductive unfolding mechanism of spike protein to guide anti-virus activities International-presentation

    Kanemura S., Okumura M.

    International Symposium on Multifaceted Protein Dynamics　2024/09/03

  18. Development of PDI family activator International-presentation

    Kuramochi T., Yamashita Y., Arai K., Kanemura S., Muraoka T., Okumura M.

    FRIS-KKU Joint Symposium 2024　2024/07/25

  19. Understanding the redox-dependent conformational and functional control of human galectin-1 International-presentation Invited

    Kanemura S., Okumura M.

    FRIS-KKU Joint Symposium 2024　2024/07/24

  20. Elucidating the reductive unfolding mechanism of spike/envelope proteins to guide anti-virus activities by disulfide-catalysts International-presentation International-coauthorship Invited

    Kanemura S., Okumura M.

    2nd-International Cross-disciplinary Symposium　2024/06/29

  21. 新興感染症に対峙するウイルスの選択的ジスルフィド結合切断酵素の理解 International-coauthorship

    金村進吾, 橋本里菜, 松崎元紀, 馬渕拓哉, 渡部マイ, 齋尾智英, 高山和雄, 李映昊, 奥村正樹

    第6回遅延制御超分子化学研究会　2024/06/19

  22. ERp57を中心とした酵素間ネットワーク解析と機能解析

    武内愛留, 松﨑元紀, 齋尾智英, 稲葉謙次, 金村進吾, 奥村正樹

    第6回遅延制御超分子化学研究会　2024/06/19

  23. フォールディング初期におけるPDI familyによるBPTIの触媒機構

    石井琴音, 金村進吾, 久米田博之, 松﨑元紀, 富田峻介, 林雨曦, 李映昊, 齋尾智英, 奥村正樹

    第6回遅延制御超分子化学研究会　2024/06/19

  24. PDI familyの活性促進剤

    倉持円来, 山下有希乃, 荒井堅太, 金村進吾, 村岡貴博, 奥村正樹

    第6回遅延制御超分子化学研究会　2024/06/19

  25. 小胞体局在酵素の相分離制御に対する活性酸素種および活性窒素種の影響

    渡部マイ, 金村進吾, 鈴木琴乃, 坂和範, 佐藤伸一, 松﨑元紀, 稲葉謙次, 中林孝和, 李映昊, 齋尾智英, 奥村正樹

    第6回遅延制御超分子化学研究会　2024/06/19

  26. Boosting the enzymatic activity of Protein Disulfide Isomerase family International-presentation

    Kuramochi T., Yamashita Y., Arai K., Kanemura S., Muraoka T., Okumura M.

    2024 Joint Conference - Korean Society for Protein Science (KSPS) & Protein Science Society of Japan (PSSJ)　2024/06/15

  27. Effects of ROS/RNS on the droplet formation of the ER-resident enzyme International-presentation

    Watabe M., Kanemura S., Suzuki K., Ban K., Sato S., Matsusaki M., Inaba K., Nakabayashi T., Lee Y -H., Saio T., Okumura M.

    2024 Joint Conference - Korean Society for Protein Science (KSPS) & Protein Science Society of Japan (PSSJ)　2024/06/15

  28. 細胞外酸化還元酵素によるウイルス感染抑制機構の解明

    金村進吾, 橋本里菜, 松崎元紀, 馬渕拓哉, 渡部マイ, 齋尾智英, 高山和雄, 李映昊, 奥村正樹

    第24回日本蛋白質科学会年会　2024/06/13

  29. PDIファミリー酵素による前駆体タンパク質プロウログアニリンのフォールディング制御機構の解明

    石井琴音, 金村進吾, 島本茂, 久米田博之, 日高雄二, 稲葉謙次, 齋尾智英, 奥村正樹

    第24回日本蛋白質科学会年会　2024/06/11

  30. PDI familyが制御する小胞体内プロインスリンの品質管理機構の理解

    倉持円来, 荒井堅太, 稲葉謙次, 金村進吾, 奥村正樹

    第24回日本蛋白質科学会年会　2024/06/11

  31. 小胞体局在酵素ERp57を中心としたタンパク質品質管理機構の解明

    武内愛留, 松﨑元紀, 齋尾智英, 稲葉謙次, 金村進吾, 奥村正樹

    第24回日本蛋白質科学会年会　2024/06/11

  32. 小胞体局在酵素の相分離制御に対する活性酸素種および活性窒素種の影響

    渡部マイ, 金村進吾, 鈴木琴乃, 坂和範, 佐藤伸一, 松﨑元紀, 稲葉謙次, 中林孝和, 李映昊, 齋尾智英, 奥村正樹

    第24回日本蛋白質科学会年会　2024/06/11

  33. 探求心：私の研究とキャリア Invited

    金村進吾

    第4回蛋白質科学会 若手の会研究交流会　2024/06/10

  34. 細胞内外におけるレドックスの理解

    金村進吾

    第1回生化学合同研究会　2024/06/04

  35. 小胞体ストレスセンサーIRE1による活性酸素種の直接的感知と分子シャペロンによるその制御

    松﨑元紀, 金村進吾, 齋尾智英, 稲葉謙次, 奥村正樹

    日本農芸化学会2024年度大会　2024/03/26

  36. 細胞内酸化還元ホメオスタシスを制御し得る低分子アロステリックジスルフィド/ジセレニド試薬

    三神瑠美, 金村進吾, 奥村正樹, 荒井堅太

    第104回日本化学会年会　2024/03/21

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Research Projects 9

  1. 沖縄型神経原性筋萎縮症に対峙する創薬シーズの発掘 Competitive

    研究代表者, 筒井正人, 研究分担者, 金村進吾

    System: 沖縄イノベーション・エコシステム共同研究推進事業

    2023/07 - 2026/03

  2. 小胞体局在酵素によるヒトガレクチン 1 の酸化還元制御機構の解明 Competitive

    Offer Organization: 徳島大学 先端酵素学研究所

    System: 共同研究

    Institution: 東北大学

    2024/04 - 2025/03

  3. レドックスとウイルスのクロストーク研究 Competitive

    Offer Organization: (公財)加藤記念バイオサイエンス振興財団

    System: 第36回加藤記念研究助成

    Institution: 東北大学

    2025 -

  4. 細胞外におけるレドックス制御メカニズムの解明 Competitive

    Offer Organization: 公益財団法人 上原記念生命科学財団

    System: 研究奨励金

    Institution: 関西学院大学

    2023/02 - 2024/03

  5. Structural basis for recognition and regulation of protein folding intermediate by molecular chaperones in the endoplasmic reticulum Competitive

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Institution: The University of Tokushima

    2020/10 - 2023/03

  6. Understanding the molecular mechanism by which PDI family catalyze oxidative protein folding of nascent chains Competitive

    Kanemura Shingo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Kwansei Gakuin University

    2019/04 - 2022/03

    More details Close

    Oxidative protein folding, which is essential for protein function, is catalyzed by PDI family enzymes. This study revealed that the secondary structure of proteins promotes the formation of native disulfide bonds in the folding. Furthermore, the structural and functional correlations of the PDI family enzymes ERp57, P5 and PDI oxidase GPx7/8 were clarified. Thus, we elucidated a part of the protein quality control network in the endoplasmic reticulum.

  7. PDIファミリー酵素による新生鎖の酸化的フォールディング及びアッセンブリーの触媒機構の解明 Competitive

    Offer Organization: 公益財団法人 内藤記念科学振興財団

    System: 内藤記念科学奨励金・研究助成

    Institution: 関西学院大学

    2020 - 2021

  8. 新生鎖の翻訳伸長反応に伴うジスルフィド結合形成機構の解明 Competitive

    金村 進吾

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 研究活動スタート支援

    2017/10 - 2019/03

  9. 新規ＰＤＩ酸化酵素ＧＰｘ７／８を起点としたジスルフィド結合形成経路の分子構造基盤 Competitive

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows

    Category: Grant-in-Aid for JSPS Fellows

    Institution: Tohoku University

    2015/04 - 2017/03

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Teaching Experience 7

  1. Biology A - Essential Cell Biology　Tohoku University

  2. Physical Chemistry Experiment　Kwansei Gakuin University

  3. Basic Chemistry Experiment II　Kwansei Gakuin University

  4. Basic Chemistry Experiment I　Kwansei Gakuin University

  5. Chemical Exercises IV　Kwansei Gakuin University

  6. Chemical Exercises III　Kwansei Gakuin University

  7. Chemical Exercises II　Kwansei Gakuin University

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