Details of the Researcher

PHOTO

Mihoko Ui
Section
Graduate School of Medicine
Job title
Assistant Professor
Degree

  • 博士（生命科学）（東京大学）

  • 修士（薬学）（東北大学）

Papers 18

  1. Design of Cyborg Proteins by Loop Region Replacement with Oligo(ethylene glycol): Exploring Suitable Mutations for Cyborg Protein Construction Using Machine Learning Peer-reviewed

    Wijak Yospanya, Akari Matsumura, Yukihiro Imasato, Tomoyuki Itou, Yusuke Aoki, Hikaru Nakazawa, Takashi Matsui, Takeshi Yokoyama, Mihoko Ui, Mitsuo Umetsu, Satoru Nagatoishi, Kouhei Tsumoto, Yoshikazu Tanaka, Kazushi Kinbara

    Bulletin of the Chemical Society of Japan　2024/09/02

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/bulcsj/uoae090 　

    ISSN： 0009-2673

    eISSN： 1348-0634

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    Abstract We synthesized a “cyborg protein,” wherein a synthetic molecule partially substitutes the main peptide chain by linking two protein domains with a synthetic oligomer. Green fluorescent protein (GFP) served as the model for constructing the cyborg proteins. We prepared circularly permuted GFP (cpGFP) with new termini between β10 and β11, where the original N- and C-termini were linked by a cleavable peptide loop. The cyborg GFP was constructed from cpGFP by linking the β10 and β11 with oligo(ethylene glycol) using maleimide-cysteine couplings, followed by the enzymatic cleavage of the N- and C-termini linking loop by thrombin. With the help of machine learning, we were able to obtain the cpGFP mutants that significantly alter the fluorescence activity (53% increase) by thrombin treatment, which splits cpGFP into two fragments (fragmented-GFP), and by heat shock. When the cyborg GFP was constructed using this mutant, the fluorescence intensity increased by 13% after heat treatment, similar to cpGFP (33% increase), and the behavior was significantly different from that of the fragmented-GFP. This result suggests the possibility that the oligo(ethylene glycol) chain in the cyborg protein plays a similar role to the peptide in the main chain of the protein.

  2. Amphiphilic structured PEG derivatives suppressing protein thermal aggregation at extremely low molecular ratio

    Adam Wawro, Takahiro Muraoka, Wijak Yospanya, Mayu Kawame, Yudai Nakagawa, Mihoko Ui, Pawel Antonik, Peter Crowley, Kouhei Tsumoto, Kazushi Kinbara

    2023/02/09

    Publisher: American Chemical Society (ACS)

    DOI： 10.26434/chemrxiv-2023-439sw 　

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    Amphiphilic structured PEG derivatives consisting of octa(ethylene glycol) chains connected with aromatic vertices inhibited the thermally-induced lysozyme aggregation even when present at below 0.1 mM concentration. This concentration range is close to a 1:1 molar ratio with the additive and lysozyme, and was completely inaccessible for previously reported stabilizers. The possible mechanisms of the stabilizing actions revealed that the PEG-based amphiphiles do not in fact prevent aggregation at the molecular level, as assumed before, but rather prevent macroscopic precipitation of the denatured protein molecules and enable dissolution of them to the native, folded state at ambient temperature. The stabilizers do not interact with properly folded native lysozyme and therefore do not affect its natural catalytic properties, indicating a potential for practical use in protein-based therapeutics.

  3. Protein encapsulation in the hollow space of hemocyanin crystals containing a covalently conjugated ligand. International-journal

    Tsubasa Hashimoto, Yuxin Ye, Mihoko Ui, Tomohisa Ogawa, Takashi Matsui, Yoshikazu Tanaka

    Biochemical and biophysical research communications　514　(1)　31-36　2019/06/18

    DOI： 10.1016/j.bbrc.2019.04.062 　

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    Encapsulation of guest molecules into the vacant space of biomacromolecular crystals has been utilized for various purposes including functioning as a protein container to protect against physical stress and structural determination of the guest. Todarodes pacificus hemocyanin (TpHc) is a hollow cylindrical decameric protein complex with an inner space 110 Å in diameter and 160 Å in height. In the crystal, TpHc forms a straw-like bundle and contains one reactive Cys (Cys3246) in the inner domain of each protomer. Here, we conjugated biotin onto Cys3246 of TpHc followed by incubation with streptavidin. The streptavidin was immobilized into the inner space of TpHc due to its interaction with biotin. Moreover, the complex containing TpHc and streptavidin was crystallized under the same conditions used for unmodified TpHc. In order to expand this methodology for a variety of proteins, we conjugated the ligand nitrilotriacetic acid (NTA) chelated to a Ni2+ ion (Ni2+-NTA) to TpHc. We found that His-tagged green fluorescent protein (GFP) was encapsulated into the Ni2+-NTA-conjugated TpHc via the interaction between the His-tag and the Ni2+-NTA group. X-ray crystallography demonstrated that the crystal packing of the complex containing TpHc and GFP was identical to that of the unmodified TpHc. Our guest immobilization method is distinct from previous approaches that are dependent on diffusion of the guest into the host crystal. Thus, our findings may accelerate the development of proteinaceous crystal engineering.

  4. Development of an Engineered Photoactive Yellow Protein as a Cross-_Linking Junction for Construction of Photoresponsive Protein-_Polymer Conjugates Peer-reviewed

    Ui, Mihoko, Miyauchi, Yusuke, Inoue, Masataka, Murakami, Makoto, Araki, Yasuyuki, Wada, Takehiko, Kinbara, Kazushi

    ChemPhotoChem　3　(6)　356-360　2019/06

    DOI： 10.1002/cptc.201900024 　

    ISSN： 2367-0932

  5. Protein stabilization by an amphiphilic short monodisperse oligo(ethylene glycol) Peer-reviewed

    Nabanita Sadhukhan, Takahiro Muraoka, Mihoko Ui, Satoru Nagatoishi, Kouhei Tsumoto, Kazushi Kinbara

    CHEMICAL COMMUNICATIONS　51　(40)　8457-8460　2015

    DOI： 10.1039/c4cc10301g 　

    ISSN： 1359-7345

    eISSN： 1364-548X

  6. Thermal-aggregation suppression of proteins by a structured PEG analogue: Importance of denaturation temperature for effective aggregation suppression Peer-reviewed

    Takahiro Muraoka, Nabanita Sadhukhan, Mihoko Ui, Shunichi Kawasaki, Enrikko Flazemi, Kota Adachi, Kazushi Kinbara

    BIOCHEMICAL ENGINEERING JOURNAL　86　41-48　2014/05

    DOI： 10.1016/j.bej.2014.03.001 　

    ISSN： 1369-703X

    eISSN： 1873-295X

  7. Grafting synthetic transmembrane units to the engineered low-toxicity alpha-hemolysin to restore its hemolytic activity Peer-reviewed

    Mihoko Ui, Kousuke Harima, Toshiaki Takei, Kouhei Tsumoto, Kazuhito V. Tabata, Hiroyuki Noji, Sumire Endo, Kimio Akiyama, Takahiro Muraoka, Kazushi Kinbara

    MOLECULAR BIOSYSTEMS　10　(12)　3199-3206　2014

    DOI： 10.1039/c4mb00405a 　

    ISSN： 1742-206X

    eISSN： 1742-2051

  8. Mutations for decreasing the immunogenicity and maintaining the function of core streptavidin. International-journal Peer-reviewed

    Kyohei Yumura, Mihoko Ui, Hirofumi Doi, Takao Hamakubo, Tatsuhiko Kodama, Kouhei Tsumoto, Akira Sugiyama

    Protein science : a publication of the Protein Society　22　(2)　213-21　2013/02

    DOI： 10.1002/pro.2203 　

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    The defining property of core streptavidin (cSA) is not only its high binding affinity for biotin but also its pronounced thermal and chemical stability. Although potential applications of these properties including therapeutic methods have prompted much biological research, the high immunogenicity of this bacterial protein is a key obstacle to its clinical use. To this end, we have successfully constructed hypoimmunogenic cSA muteins in a previous report. However, the effects of these mutations on the physicochemical properties of muteins were still unclear. These mutations retained the similar electrostatic charges to those of wild-type (WT) cSA, and functional moieties with similar hydrogen bond pattern. Herein, we performed isothermal titration calorimetry, differential scanning calorimetry, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis to gain insight into the physicochemical properties and functions of these modified versions of cSA. The results indicated that the hypoimmunogenic muteins retained the biotin-binding function and the tetramer structure of WT cSA. In addition, we discuss the potential mechanisms underlying the success of these mutations in achieving both immune evasion and retention of function; these mechanisms might be incorporated into a new strategy for constructing hypoimmunogenic proteins.

  9. A Structured Monodisperse PEG for the Effective Suppression of Protein Aggregation Peer-reviewed

    Takahiro Muraoka, Kota Adachi, Mihoko Ui, Shunichi Kawasaki, Nabanita Sadhukhan, Haruki Obara, Hidehito Tochio, Masahiro Shirakawa, Kazushi Kinbara

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION　52　(9)　2430-2434　2013

    DOI： 10.1002/anie.201206563 　

    ISSN： 1433-7851

  10. Application of photoactive yellow protein as a photoresponsive module for controlling hemolytic activity of staphylococcal alpha-hemolysin Peer-reviewed

    Mihoko Ui, Yoshikazu Tanaka, Yasuyuki Araki, Takehiko Wada, Toshiaki Takei, Kouhei Tsumoto, Sumire Endo, Kazushi Kinbara

    CHEMICAL COMMUNICATIONS　48　(39)　4737-4739　2012

    DOI： 10.1039/c2cc18118e 　

    ISSN： 1359-7345

    eISSN： 1364-548X

  11. Amplification of Light-induced Molecular-Shape Change by Supramolecular Machines

    Mihoko Ui, Yoshikazu Tanaka, Kazushi Kinbara

    JOURNAL OF PHOTOPOLYMER SCIENCE AND TECHNOLOGY　25　(5)　655-658　2012

    DOI： 10.2494/photopolymer.25.655 　

    ISSN： 0914-9244

  12. Structural and energetic hot-spots for the interaction between a ladder-like polycyclic ether and the anti-ciguatoxin antibody 10C9Fab Peer-reviewed

    Mihoko Ui, Yoshikazu Tanaka, Takeshi Tsumuraya, Ikuo Fujii, Masayuki Inoue, Masahiro Hirama, Kouhei Tsumoto

    MOLECULAR BIOSYSTEMS　7　(3)　793-798　2011

    DOI： 10.1039/c0mb00162g 　

    ISSN： 1742-206X

    eISSN： 1742-2051

  13. An approach to rational ligand-design based on a thermodynamic analysis Peer-reviewed

    Mihoko Ui, Kouhei Tsumoto

    Recent Patents on Biotechnology　4　(3)　183-188　2010

    DOI： 10.2174/187220810793611482 　

    ISSN： 1872-2083

  14. How protein recognizes ladder-like polycyclic ethers - Interactions between ciguatoxin (CTX3C) fragments and its specific antibody 10C9 Peer-reviewed

    Mihoko Ui, Yoshikazu Tanaka, Takeshi Tsumuraya, Ikuo Fujii, Masayuki Inoue, Masahiro Hirama, Kouhei Tsumoto

    JOURNAL OF BIOLOGICAL CHEMISTRY　283　(28)　19440-19447　2008/07

    DOI： 10.1074/jbc.M801282200 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  15. Critical contribution of aromatic rings to specific recognition of polyether rings - The case of ciguatoxin CTX3C-ABC and its specific antibody 1C49 Peer-reviewed

    Kouhei Tsumoto, Akiko Yokota, Yoshikazu Tanaka, Mihoko Ui, Takeshi Tsumuraya, Ikuo Fujii, Izumi Kumagai, Yoko Nagumo, Hiroki Oguri, Masayuki Inoue, Masahiro Hirama

    JOURNAL OF BIOLOGICAL CHEMISTRY　283　(18)　12259-12266　2008/05

    DOI： 10.1074/jbc.M710553200 　

    ISSN： 0021-9258

  16. 1P-057 Molecular recognition mechanism of an anti-ciguatoxin antibody : mutational study and small-molecule binding screen(The 46th Annual Meeting of the Biophysical Society of Japan)

    Ui Mihoko, Tanaka Yoshikazu, Tsumuraya Takeshi, Fujii Ikuo, Inoue Masayuki, Hirama Masahiro, Tsumoto Kouhei

    Seibutsu Butsuri　48　S29-S30　2008

    Publisher: The Biophysical Society of Japan General Incorporated Association

    DOI： 10.2142/biophys.48.S29_5 　

  17. Pyrene-appended alpha-cyclodextrin as a fluorescent pH probe responding to a wide range Peer-reviewed

    Suzuki, I, M Ui, A Yamauchi

    ANALYTICAL SCIENCES　22　(5)　655-657　2006/05

    DOI： 10.2116/analsci.22.655 　

    ISSN： 0910-6340

  18. Supramolecular probe for bicarbonate exhibiting anomalous pyrene fluorescence in aqueous media. Peer-reviewed

    Iwao Suzuki, Mihoko Ui, Akiyo Yamauchi

    Journal of the American Chemical Society　127　4498-4499　2006

    DOI： 10.1021/ja055772f 　

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Misc. 19

  1. Protein Cyborgization by Main Chain Substitution

    AOKI Yusuke, UI Mihoko, MATSUI Takashi, TANAKA Yoshikazu, MURAOKA Takahiro, SATO Kohei, KINBARA Kazushi

    日本化学会春季年会講演予稿集(CD-ROM)　99th　2019

  2. 光機能性材料開発に向けた光応答蛋白質‐親水性高分子複合体の構築

    宇井美穂子, 宮内佑輔, 村上慎, 荒木保幸, 和田健彦, 金原数

    日本化学会春季年会講演予稿集(CD-ROM)　97th　ROMBUNNO.2PB‐156　2017/03/03

  3. Construction of photoresponsive protein‐polymer conjugates based on a junctional photoractive yellow protein

    宇井美穂子, 宮内佑輔, 村上慎, 荒木保幸, 和田健彦, 金原数

    化学系学協会東北大会プログラムおよび講演予稿集　2016　117　2016/09/10

  4. 改変型光受容蛋白質PYPの機能性材料への展開

    宇井美穂子, 宮内佑輔, 村上慎, 荒木保幸, 和田健彦, 金原数

    東北大学多元物質科学研究所研究発表会講演予稿集　16th　54　2016

  5. 光応答性タンパク質の特性を利用した機能性材料の創製

    前島辰哉, 宇井美穂子, 荒木保幸, 和田健彦, 金原数

    日本化学会講演予稿集　95th　(3)　951　2015/03/11

    ISSN： 0285-7626

  6. 改変型光応答性タンパク質モジュールを利用したソフトマテリアルの創製

    宮内佑輔, 宇井美穂子, 村上慎, 荒木保幸, 和田健彦, 金原数

    日本化学会講演予稿集　94th　(3)　973　2014/03/12

    ISSN： 0285-7626

  7. 光応答性phosphodiesteraseの構築と生体機能光制御への応用

    宇井美穂子, 新井康広, 村上慎, 荒木保幸, 和田健彦, 高橋泰人, 金原数

    日本化学会講演予稿集　94th　(3)　921　2014/03/12

    ISSN： 0285-7626

  8. cAMPの可逆制御を目指した光応答性PDEの創製

    新井康広, 宇井美穂子, 村上慎, 荒木保幸, 和田健彦, 高橋泰人, 金原数

    日本化学会講演予稿集　93rd　(3)　1002　2013/03/08

    ISSN： 0285-7626

  9. 光応答性分子を用いた孔形成毒素alpha‐hemolysinの光制御系の構築

    宇井美穂子, 播磨耕祐, 田中良和, 荒木保幸, 和田健彦, 武井俊朗, 津本浩平, 金原数

    バイオ・高分子シンポジウム講演要旨集　22nd　11-12　2012/06/15

    ISSN： 0917-5202

  10. 光受容蛋白質Phtoactive Yellow proteinを用いたStaphylococcal alpha‐Hemolysinの溶血活性制御

    宇井美穂子, 田中良和, 荒木保幸, 和田健彦, 武井俊朗, 津本浩平, 金原数

    高分子学会予稿集(CD-ROM)　61　(1)　ROMBUNNO.1H31　2012/05/15

  11. 人工分子を用いたStaphylococcus aureus α‐hemolysinの溶血活性の制御

    播磨耕祐, 宇井美穂子, 田中良和, 石井則行, 金原数

    日本化学会講演予稿集　92nd　(3)　776　2012/03/09

    ISSN： 0285-7626

  12. 光応答性蛋白質Phtoactive Yellow protein融合Staphylococcal alpha‐Hemolysinの機能制御

    宇井美穂子, 田中良和, 荒木保幸, 和田健彦, 武井俊朗, 津本浩平, 金原数

    日本化学会講演予稿集　92nd　(3)　816　2012/03/09

    ISSN： 0285-7626

  13. 光応答性タンパク質PYP融合によるStaphylococcal α‐Hemolysinの光制御

    宇井美穂子, 田中良和, 荒木保幸, 和田健彦, 武井俊朗, 津本浩平, 金原数

    東北大学多元物質科学研究所研究発表会講演予稿集　11th　23　2011

  14. Rational Fragment-design Method Based on a Thermodynamic Analysis

    Kouhei Tsumoto, Mihoko Ui

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　129　(11)　1311-1317　2009/11

    ISSN： 0031-6903

  15. [Recognition mechanism for poly-cyclic ether toxin by anti-ciguatoxin antibody]. Peer-reviewed

    Ui M, Tsumoto K

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme　54　(9)　1182-1189　2009/07

    Publisher: 共立出版

    ISSN： 0039-9450

  16. 抗体による環状ポリエーテル系毒素シガトキシンの認識と識別

    宇井美穂子, 津本浩平

    蛋白質核酸酵素　54　1182-1189　2009

  17. 抗原抗体相互作用の熱力学的解析：特異性と親和性

    津本浩平, 宇井美穂子

    熱測定　36　205-215　2009

  18. 相互作用の熱力学情報に基づく低分子リガンド設計

    津本浩平, 宇井美穂子

    薬学雑誌　2009

    DOI： 10.1248/yakushi.129.1311 　

  19. 2P047 The structural and thermodynamic analysis of the interaction between ciguatoxin and its Antibody 10C9 Fab(Proteins-structure and structure-function relationship,Poster Presentations)

    Ui Mihoko, Tanaka Yoshikazu, Tsumuraya Takeshi, Fujii Ikuo, Inoue Masayuki, Hirama Masahiro, Tsumoto Kouhei

    Seibutsu Butsuri　47　(0)　S124　2007

    Publisher: 一般社団法人 日本生物物理学会

    DOI： 10.2142/biophys.47.S124_4 　

    ISSN： 0582-4052

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Research Projects 2

  1. Development of a photoresponsive module for protein photoregulation

    Ui Mihoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2013/04/01 - 2016/03/31

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    Light has been considered as an effective tool to regulate biomolecules due to its high spatiotemporal resolution and noninvasive properties. In this study, we developed photoresponsive modules based on photoreceptor PYP by providing an unnatural amino acid bearing a chemically reactive group instead of methionine. The engineered PYP was coupled with the hydrophilic copolymer, resulting in generation of photoresponsive protein-polymer conjugates. The viscosity of the resulting conjugate was reversibly decreased by blue light irradiation. This material would possibly be applicable for construction of photoresponsive biomaterials and also broaden the potential of engineered PYP as a photoresponsive module for optical regulation of molecules.

  2. Construction of a photoregulating system for self-assembly proteins

    UI Mihoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2011 - 2012

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    We constructed two types of photo-controlled nano-pore devices based on PYP photoreceptor-fused staphylococcal pore-forming toxin alpha-hemolysin. The both PYP-fused devices had the similar photocycle as wild type PYP and inhibited the transmission efficiency of ions through the sheep red blood cells membrane under light irradiation. These PYP-fused devices will serve molecular basis for nano-pore devices of which activity is easy to be arbitrarily tuned by light irradiation.