Tokushima University / Educator and Researcher Directory --- Kawagoe, Soichiro

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Tokushima University ⟩ Institute of Advanced Medical Sciences ⟩ 基幹研究部門 ⟩

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Research

Personal Web Page

https://researchmap.jp/skawagoe (researchmap)

https://orcid.org/0000-0002-7158-4504 (ORCID)

Field of Study

○	Life sciences [Biophysics]
○	Life sciences [Structural biochemistry]

Subject of Study

Book / Paper

(See https://researchmap.jp/skawagoe (researchmap) for Published Book / Papers / Presentations.)

Academic Paper (Judged Full Paper):

1.	Yoshikazu Hattori, Munehiro Kumashiro, Hiroyuki Kumeta, Taisei Kyo, Soichiro Kawagoe, Motonori Matsusaki and Tomohide Saio : A Disease-Associated Mutation Impedes PPIA through Allosteric Dynamics Modulation, Biochemistry, 64, 14, 2971-2975, 2025. (Link to Publication Site) ● Publication site (DOI): 10.1021/acs.biochem.5c00260 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-105009433118 (DOI: 10.1021/acs.biochem.5c00260, Elsevier: Scopus)
2.	Soichiro Kawagoe, Motonori Matsusaki, Takuya Mabuchi, Yuto Ogasawara, Kazunori Watanabe, Koichiro Ishimori and Tomohide Saio : Mechanistic Insights Into Oxidative Response of Heat Shock Factor 1 Condensates, JACS Au, 5, 2, 606-617, 2025. (Keyword) biological phase transition / biophysics / heat shock factor 1 / oxidative hyper-oligomerization / stress response (Link to Publication Site) ● Publication site (DOI): 10.1021/jacsau.4c00578 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85216615817 (DOI: 10.1021/jacsau.4c00578, Elsevier: Scopus)
3.	Saori Yoshimura, Ryuki Shimada, Koji Kikuchi, Soichiro Kawagoe, Hironori Abe, Sakie Iisaka, Sayoko Fujimura, Kei-Ichiro Yasunaga, Shingo Usuki, Naoki Tani, Takashi Ohba, Eiji Kondoh, Tomohide Saio, Kimi Araki and Kei-Ichiro Ishiguro : Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions., Nature Communications, 15, 1, 3330, 2024. (Summary) Meiotic prophase progression is differently regulated in males and females. In males, pachytene transition during meiotic prophase is accompanied by robust alteration in gene expression. However, how gene expression is regulated differently to ensure meiotic prophase completion in males remains elusive. Herein, we identify HSF5 as a male germ cell-specific heat shock transcription factor (HSF) for meiotic prophase progression. Genetic analyzes and single-cell RNA-sequencing demonstrate that HSF5 is essential for progression beyond the pachytene stage under non-stress conditions rather than heat stress. Chromatin binding analysis in vivo and DNA-binding assays in vitro suggest that HSF5 binds to promoters in a subset of genes associated with chromatin organization. HSF5 recognizes a DNA motif different from typical heat shock elements recognized by other canonical HSFs. This study suggests that HSF5 is an atypical HSF that is required for the gene expression program for pachytene transition during meiotic prophase in males. (Keyword) Female / Male / Mice / Heat Shock Transcription Factors / Heat-Shock Response / Meiotic Prophase I / Mice, Inbred C57BL / Mice, Knockout / Spermatogenesis / Testis / Animals (Tokushima University Institutional Repository) ● Metadata: 2012857 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41467-024-47601-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38684656 ● Search Scopus @ Elsevier (PMID): 38684656 ● Search Scopus @ Elsevier (DOI): 10.1038/s41467-024-47601-0 (Tokushima University Institutional Repository: 2012857, DOI: 10.1038/s41467-024-47601-0, PubMed: 38684656)
4.	Soichiro Kawagoe, Munehiro Kumashiro, Takuya Mabuchi, Hiroyuki Kumeta, Koichiro Ishimori and Tomohide Saio : Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe., Biochemistry, 61, 24, 2897-2908, 2022. (Summary) A transcriptional regulatory system called heat shock response (HSR) has been developed in eukaryotic cells to maintain proteome homeostasis under various stresses. Heat shock factor-1 (Hsf1) plays a central role in HSR, mainly by upregulating molecular chaperones as a transcription factor. Hsf1 forms a complex with chaperones and exists as a monomer in the resting state under normal conditions. However, upon heat shock, Hsf1 is activated by oligomerization. Thus, oligomerization of Hsf1 is considered an important step in HSR. However, the lack of information about Hsf1 monomer structure in the resting state, as well as the structural change via oligomerization at heat response, impeded the understanding of the thermosensing mechanism through oligomerization. In this study, we applied solution biophysical methods, including fluorescence spectroscopy, nuclear magnetic resonance, and circular dichroism spectroscopy, to investigate the heat-induced conformational transition mechanism of Hsf1 leading to oligomerization. Our study showed that Hsf1 forms an inactive closed conformation mediated by intramolecular contact between leucine zippers (LZs), in which the intermolecular contact between the LZs for oligomerization is prevented. As the temperature increases, Hsf1 changes to an open conformation, where the intramolecular LZ interaction is dissolved so that the LZs can form intermolecular contacts to form oligomers in the active form. Furthermore, since the interaction sites with molecular chaperones and nuclear transporters are also expected to be exposed in the open conformation, the conformational change to the open state can lead to understanding the regulation of Hsf1-mediated stress response through interaction with multiple cellular components. (Keyword) DNA-Binding Proteins / Heat Shock Transcription Factors / Tryptophan / Molecular Chaperones / Heat-Shock Response (Link to Publication Site) ● Publication site (DOI): 10.1021/acs.biochem.2c00492 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36485006 ● Search Scopus @ Elsevier (PMID): 36485006 ● Search Scopus @ Elsevier (DOI): 10.1021/acs.biochem.2c00492 (DOI: 10.1021/acs.biochem.2c00492, PubMed: 36485006)
5.	Shuhei Yoshida, Shota Uehara, Noriyasu Kondo, Yu Takahashi, Shiho Yamamoto, Atsushi Kameda, Soichiro Kawagoe, Naoko Inoue, Masami Yamada, Norito Yoshimura and Yuki Tachibana : Peptide-to-Small Molecule: A Pharmacophore-Guided Small Molecule Lead Generation Strategy from High-Affinity Macrocyclic Peptides., Journal of Medicinal Chemistry, 65, 15, 10655-10673, 2022. (Summary) Recent technological innovations have led to the development of methods for the rapid identification of high-affinity macrocyclic peptides for a wide range of targets; however, it is still challenging to achieve the desired activity and membrane permeability at the same time. Here, we propose a novel small molecule lead discovery strategy, Peptide-to-Small Molecule, which is a combination of rapid identification of high-affinity macrocyclic peptides via peptide display screening followed by pharmacophore-guided de novo design of small molecules, and demonstrate the applicability using nicotinamide N-methyltransferase (NNMT) as a target. Affinity selection by peptide display technology identified macrocyclic peptide 1 that exhibited good enzymatic inhibitory activity but no cell-based activity. Thereafter, a peptide pharmacophore-guided de novo design and further structure-based optimization resulted in highly potent and cell-active small molecule 14 (cell-free IC50 = 0.0011 μM, cell-based IC50 = 0.40 μM), indicating that this strategy could be a new option for drug discovery. (Keyword) Cell Membrane Permeability / Drug Discovery / Peptides (Link to Publication Site) ● Publication site (DOI): 10.1021/acs.jmedchem.2c00919 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35904556 ● Search Scopus @ Elsevier (PMID): 35904556 ● Search Scopus @ Elsevier (DOI): 10.1021/acs.jmedchem.2c00919 (DOI: 10.1021/acs.jmedchem.2c00919, PubMed: 35904556)
6.	Soichiro Kawagoe, Hiroshi Nakagawa, Hiroyuki Kumeta, Koichiro Ishimori and Tomohide Saio : Structural insight into proline cis/ trans isomerization of unfolded proteins catalyzed by the trigger factor chaperone, The Journal of Biological Chemistry, 293, 39, 15095-15106, 2018. (Summary) Molecular chaperones often possess functional modules that are specialized in assisting the formation of specific structural elements, such as a disulfide bridges and peptidyl-prolyl bonds in cis form, in the client protein. A ribosome-associated molecular chaperone trigger factor (TF), which has a peptidyl-prolyl cis/trans isomerase (PPIase) domain, acts as a highly efficient catalyst in the folding process limited by peptidyl-prolyl isomerization. Herein we report a study on the mechanism through which TF recognizes the proline residue in the unfolded client protein during the cis/trans isomerization process. The solution structure of TF in complex with the client protein showed that TF recognizes the proline-aromatic motif located in the hydrophobic stretch of the unfolded client protein through its conserved hydrophobic cleft, which suggests that TF preferentially accelerates the isomerization of the peptidyl-prolyl bond that is eventually folded into the core of the protein in its native fold. Molecular dynamics simulation revealed that TF exploits the backbone amide group of Ile195 to form an intermolecular hydrogen bond with the carbonyl oxygen of the amino acid residue preceding the proline residue at the transition state, which presumably stabilizes the transition state and thus accelerates the isomerization. The importance of such intermolecular hydrogen-bond formation during the catalysis was further corroborated by the activity assay and NMR relaxation analysis. (Keyword) Protein Conformation (Link to Publication Site) ● Publication site (DOI): 10.1074/jbc.RA118.003579 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30093407 ● Search Scopus @ Elsevier (PMID): 30093407 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.RA118.003579 (DOI: 10.1074/jbc.RA118.003579, PubMed: 30093407)
7.	Tomohide Saio, Soichiro Kawagoe, Koichiro Ishimori and G Charalampos Kalodimos : Oligomerization of a molecular chaperone modulates its activity., eLife, 7, e35731, 2018. (Summary) Molecular chaperones alter the folding properties of cellular proteins via mechanisms that are not well understood. Here, we show that Trigger Factor (TF), an ATP-independent chaperone, exerts strikingly contrasting effects on the folding of non-native proteins as it transitions between a monomeric and a dimeric state. We used NMR spectroscopy to determine the atomic resolution structure of the 100 kDa dimeric TF. The structural data show that some of the substrate-binding sites are buried in the dimeric interface, explaining the lower affinity for protein substrates of the dimeric compared to the monomeric TF. Surprisingly, the dimeric TF associates faster with proteins and it exhibits stronger anti-aggregation and holdase activity than the monomeric TF. The structural data show that the dimer assembles in a way that substrate-binding sites in the two subunits form a large contiguous surface inside a cavity, thus accounting for the observed accelerated association with unfolded proteins. Our results demonstrate how the activity of a chaperone can be modulated to provide distinct functional outcomes in the cell. (Keyword) Binding Sites / Escherichia coli / Escherichia coli Proteins / Molecular Chaperones / Peptidylprolyl Isomerase / Protein Binding / Protein Conformation / Protein Folding / Protein Multimerization (Link to Publication Site) ● Publication site (DOI): 10.7554/eLife.35731 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29714686 ● Summary page in Scopus @ Elsevier: 2-s2.0-85051931685 (DOI: 10.7554/eLife.35731, PubMed: 29714686, Elsevier: Scopus)

Review, Commentary:

1.	Soichiro Kawagoe, Koichiro Ishimori and Tomohide Saio : Structural and Kinetic Views of Molecular Chaperones in Multidomain Protein Folding., International Journal of Molecular Sciences, 23, 5, Feb. 2022. (Summary) Despite recent developments in protein structure prediction, the process of the structure formation, folding, remains poorly understood. Notably, folding of multidomain proteins, which involves multiple steps of segmental folding, is one of the biggest questions in protein science. Multidomain protein folding often requires the assistance of molecular chaperones. Molecular chaperones promote or delay the folding of the client protein, but the detailed mechanisms are still unclear. This review summarizes the findings of biophysical and structural studies on the mechanism of multidomain protein folding mediated by molecular chaperones and explains how molecular chaperones recognize the client proteins and alter their folding properties. Furthermore, we introduce several recent studies that describe the concept of kinetics-activity relationships to explain the mechanism of functional diversity of molecular chaperones. (Keyword) Humans / Kinetics / Molecular Chaperones / Protein Folding (Tokushima University Institutional Repository) ● Metadata: 2011035 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms23052485 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35269628 ● Summary page in Scopus @ Elsevier: 2-s2.0-85125038979 (Tokushima University Institutional Repository: 2011035, DOI: 10.3390/ijms23052485, PubMed: 35269628, Elsevier: Scopus)
2.	Soichiro Kawagoe, Mori Eiichiro and Tomohide Saio : Regulation of Liquid-Liquid Phase Separation by Molecular Chaperones, Thermal Medicine, 37, 2, 31-44, Aug. 2021. (Link to Publication Site) ● Publication site (DOI): 10.3191/thermalmed.37.31 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390570408616681984 ● Search Scopus @ Elsevier (DOI): 10.3191/thermalmed.37.31 (DOI: 10.3191/thermalmed.37.31, CiNii: 1390570408616681984)

Proceeding of International Conference:

1.	Soichiro Kawagoe, Hiroyuki Kumeta and Tomohide Saio : Flipping of the tryptophan ring in the protein core probed by 19F NMR-based solvent accessibility profiling, 2025 Korea-Japan Joint Conference on Protein Science, Jun. 2025.
2.	Soichiro Kawagoe and Tomohide Saio : Structural dynamics regulating the molecular assembly of heat shock transcription factor 1, International Symposium on Multifaceted Protein Dynamics, Sep. 2024.
3.	Soichiro Kawagoe, Kumeta Hiroyuki and Tomohide Saio : Aromatic Ring Flipping in Structured Domain Modulates the Assembly of Intrinsically Disordered Region, The 30th International Conference on Magnetic Resonance in Biological Systems, Aug. 2024.

Proceeding of Domestic Conference:

1.	佐藤伸一, 小垣考弘, 闐闐孝介, 菅野杏奈, 馬渕拓哉, Tomohide Saio, 斎藤かなえ, 森陽音, 藤村千鶴, Soichiro Kawagoe, 袖岡幹子, 川北哲也 and 鈴木信幸 : タンパク質凝集プローブを活用した抗体劣化の部位レベル解析, 日本ケミカルバイオロジー学会第19回年会, Jun. 2025.
2.	Soichiro Kawagoe, 久米田博之 and Tomohide Saio : DNA結合ドメインの構造ダイナミクスによる転写因子Hsf1の液-液相分離制御, 第97回日本生化学会大会, Nov. 2024.
3.	Soichiro Kawagoe, 久米田博之 and Tomohide Saio : 転写因子Hsf1の液-液相分離を制御する DNA結合ドメインの構造平衡メカニズム, 第63回 NMR討論会, Oct. 2024.
4.	Soichiro Kawagoe : 溶液NMRを主体としたストレス応答性液-液相分離の分子機構解析, 第59回先端酵素学研究所セミナー(最先端研究者特別講演会), Jul. 2024.
5.	武井梓穂, 宇賀神魁, Soichiro Kawagoe, Tomohide Saio, 松田正, 前仲勝実, 姚閔 and 尾瀬農之 : 乳がん特異的キナーゼとアダプター蛋白質が形成する分子集合と酵素活性の相関を検証する, 第24回日本蛋白質科学会年会, Jun. 2024.
6.	Soichiro Kawagoe, 久米田博之 and Tomohide Saio : Heat shock factor-1のストレス応答性液-液相分離の構造基盤, 第24回日本蛋白質科学会年会, Jun. 2024.
7.	佐藤伸一, 闐闐孝介, 小垣考弘, 馬渕拓哉, Tomohide Saio, 菅野杏奈, Soichiro Kawagoe, 小柳恵里, 藤村千鶴, 江越脩祐, 中根啓太, 石川稔, 友重秀介, 丸吉京介, 袖岡幹子 and 鈴木信幸 : Development of chemical probes for protein aggregation and analysis of antibody aggregates, 日本ケミカルバイオロジー学会第18回年会, May 2024.
8.	Soichiro Kawagoe, 馬渕拓哉, 久米田博之, Motonori Matsusaki, 熊代宗弘, 石森浩一郎 and Tomohide Saio : Molecular mechanisms of multiple interactions regulating stress sensor assembly, 第61回日本生物物理学会年会, Nov. 2023.
9.	朱浩傑, Soichiro Kawagoe, 久米田博之, 石森浩一郎 and Tomohide Saio : タンパク質アンフォールディングを担うシャペロン複合体の構造解析, 第 62回 NMR討論会, Nov. 2023.
10.	Soichiro Kawagoe : 溶液NMR法による弱い相互作用の分子機構解析とキャリア形成, 第6回ExCELLS若手リトリート, Oct. 2023.
11.	Soichiro Kawagoe : ストレスセンサーの活性制御を担うプロミスカス相互作⽤の分⼦機構, 2023年度徳島⼤学先端酵素学研究所シンポジウム, Jul. 2023.
12.	Soichiro Kawagoe, 馬渕拓哉, 久米田博之, 熊代宗弘, 石森浩一郎 and Tomohide Saio : 局所構造形成と連動したheat shock factor-1の会合状態変化, 第23回日本蛋白質科学会年会, Jul. 2023.
13.	Soichiro Kawagoe, Motonori Matsusaki, 石森浩一郎 and Tomohide Saio : 高次多量体形成が駆動するheat shock factor-1液滴の酸化的相転移, 第 22 回日本蛋白質科学会年会, Jun. 2022.

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

Structural insight into the interaction network driving the multi-state transition of heat shock transcription factor 1 (Project/Area Number: 24K18063 )
Kinetic analysis of multivalent interaction regulating the dynamic molecular assembly (Project/Area Number: 23K19353 )
Mechanism of chaperone activity modulation through promiscuous recognitions (Project/Area Number: 23K23824 )
Search by Researcher Number (10980716)