分子シャペロンの機能解析とその応用

 

分子シャペロンは、生体内部で、タンパク質の生成・成熟・輸送・管理・分解など、非常に重要な現象に関わるタンパク質である。さらに近年、様々な疾患にも大きく関わっていることが明らかになってきた。我々のチームは、代表的な分子シャペロンのひとつであるプレフォルディンの機能を調べるとともに、様々な応用を目指し、1分子蛍光イメージングなど、最新の技術を駆使した研究を行っている。

 

 

シャペロン

分子シャペロンの機能解析とその応用

 

分子シャペロンの一つであるプレフォルディンは、新生ペプチドや、変性したタンパク質に結合し、シャペロニンに受け渡すことでタンパク質のフォールディングを助けていると考えられているが、詳しい機構は未解明であった。これまで、プレフォルディンとシャペロニンが、どのように協調して変性タンパク質のフォールディングを助けているかを調べてきた。今後は、さらなる作用機構解明と共に、疾患検出や、タンパク質の能動的品質管理など、様々な応用へ向けた研究を行っていく。

 

文献

(1)

Tamotsu Zako, Miya Yoshimoto, Hiroshi Hyodo, Hidehiro Kishimoto, Masaaki Ito, Kazuhiro Kaneko, Kohei Soga and Mizuo Maeda "Cancer-targeted Near Infrared imaging using rare earth ion-doped ceramic nanoparticles" Biomater. Sci. 3, 59-64 (2015)

(2)

Tamotsu Zako and Mizuo Maeda "Application of biomaterials for the detection of amyloid aggregates" Biomater. Sci. 2, 951-955 (2014)

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Eisuke Takai, Ken Uda, Shuhei Matsushita, Yui Shikiya, Yoichi Yamada, Tamotsu Zako, Mizuo Maeda and Kentaro Shiraki "Cysteine Inhibits Amyloid Fibrillation of the Lysozyme and Directs the Formation of Small Worm-like Aggregates through Non-Covalent Interactions" Biotech. Prog. 30, 470-478 (2014)

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Eisuke Takai, Gai Ohashi, Tomonori Yoshida, Karin M. Sorgjerd, Tamotsu Zako, Mizuo Maeda, Katsuhisa Kitano and Kentaro Shiraki "Degeneration of Amyloid-b Fibrils by Low Temperature Atmospheric Pressure Plasma in Aqueous Solution"  Appl. Phys. Lett. 104, 023701 (2014)

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Eisuke Takai, Ken Uda, Tomonori Yoshida, Tamotsu Zako, Mizuo Maeda, Yoichi Yamada and Kentaro Shiraki "Cysteine Inhibit Fibrillization and Cytotoxicity of Amyloid-beta 40 and 42: Implication for Contribution of Thiophilic Interaction” Phys. Chem. Chem. Phys. 16, 3566-3572 (2014)

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Aline C.C. Rotzetter, Christoph M. Schumacher, Tamotsu Zako, Wendelin J. Stark and Mizuo Maeda "Rapid Surface-  Biostructure Interaction Analysis using strong Metal-based Nanomagnets" Langmuir 29, 14117-14123 (2013)

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Helene Vignaud, Claude Bobo, Ioan Lascu, Karin M. Sorgjerd, Tamotsu Zako, Mizuo Maeda, Benedicte Salin, Sophie Lecomte and Christophe Cullin "A structure-toxicity study of Abeta42 reveals a new anti-parallel aggregation pathway" PLoS ONE 8, e80262 (2013)

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Tong Bu, Tamotsu Zako, Masahiro Fujita and Mizuo Maeda "Detection of DNA Induced Gold Nanoparticle Aggregation with Dark Field Imaging" Chem. Commun. 49, 7531-7533 (2013)

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Erika Tashiro, Tamotsu Zako, Hideki Muto, Yoshinori Itoo, Karin Sorgjerd, Naofumi Terada, Akira Abe, Makoto Miyazawa, Akira Kitamura, Hirotake Kitaura, Hiroshi Kubota, Mizuo Maeda, Takashi Momoi, Sanae M.M. Iguchi-Ariga, Masataka Kinjo, and Hiroyoshi Ariga "Prefoldin protects neuronal cells from polyglutamine toxicity by preventing aggregation formation"  J. Biol. Chem. 288, 19958-19972 (2013)

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Karin M Sorgjerd, Tamotsu Zako, Masafumi Sakono, Peter C Stirling, Michel R Leroux, Takashi Saito, Per Nilsson, Misaki Sekimoto, Takaomi C Saido, and Mizuo Maeda " Human Prefoldin Inhibits Amyloid-β () Fibrillation and Contributes to Formation of Nontoxic Aggregates" Biochemistry, 52, 3532-3542 (2013)

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Naofumi Terada, Tamotsu Zako and Mizuo Maeda "Photon counting histogram using numerical data of point spread function" Jpn. J. Appl. Phys. 52, 038001 (2013)

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Masafumi Sakono, Arata Utsumi, Tamotsu Zako, Tetsuya Abe, Masafumi Yohda and Mizuo Maeda, "Formation of non-toxic fibrils by small heat shock protein under heat-stress conditions" Biochem Biophys Res Commun. 430, 1259-64 (2013)

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Ryoko Watanabe-Tamaki, Atsushi Ishikawa, Takuo Tanaka, Tamotsu Zako and Mizuo Maeda, "DNA-Templating Mass Production of Gold Trimer Rings for Optical Metamaterials" J. Phys. Chem. C, 116, 15028-15033 (2012)

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Tamotsu Zako, Masafumi Sakono, Takahiro Kobayashi, Karin Sorgjerd, K. Peter R. Nilsson, Per Hammarstrom, Mikael Lindgren and Mizuo Maeda "Cell interaction study of amyloid using luminescent conjugated polythiophene: Implication that amyloid cytotoxicity is correlated with prolonged cellular binding" ChemBioChem 13, 358-363 (2012)

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Katarzyna Maria Psonka-antonczyk, Julien Duboisset, Bjorn Torger Stokke, Tamotsu Zako, Takahiro Kobayashi, Mizuo Maeda, Sofie Nystrom, Jeff Mason, Per Hammarstrom, K. Peter. R. Nilsson, Mikael Lindgren "Nanoscopic and photonic ultrastructural characterization of two distinct insulin amyloid states" Int. J. Mol. Sci. 13, 1461-1480 (2012)

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Masafumi Sakono, Tamotsu Zako, Masafumi Yohda and Mizuo Maeda "Amyloid oligomer detection by immobilized molecular chaperone" Biochem. Eng. J. 61, 28-33 (2012)

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Masafumi Sakono, Tamotsu Zako and Mizuo Maeda "Naked-eye Detection of Amyloid Aggregates using Gold Nanoparticles Modified with Amyloid Beta Antibody" Anal. Sci. 28, 73-76 (2012)

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Masafumi Sakono, Shigenori Akiyama, Tamotsu Zako, Shujiro Sakaki, Tomonori Waku, Naoki Tanaka and Mizuo Maeda "Immobilized Insulin Amyloid Enhances Cell Adhesion and Proliferation due to Interaction with Fibronectin" Chem. Lett., 40, 315-317 (2011)

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Masafumi Sakono, Shigenori Akiyama, Tamotsu Zako, Shujiro Sakaki, Tomonori Waku, Naoki Tanaka and Mizuo Maeda "Application of two morphologically different fibrillar and filamentous insulin amyloids as a biomaterial for cell culture surfaces" React. Funct. Polym. 71, 324-328 (2011)

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Masafumi Sakono, Tamotsu Zako, Srdja Drakulic, Jose M Valpuesta, Masafumi Yohda and Mizuo Maeda "Size-selective recognition of gold nanoparticles by a molecular chaperone" Chem. Phys. Lett. 501, 108-112 (2010)

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Takahito Ohshiro, Tamotsu Zako, Ryoko Wanatabe-Tamaki, Takuo Tanaka and Mizuo Maeda "A Facile Method Towards Cyclic Assembly of Gold Nanoparticles Using DNA Template Alone" Chem. Comm. 46, 6132-6134 (2010)

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Muhamad Sahlan, Taro Kanzaki,Tamotsu Zako, Mizuo Maeda and Masafumi Yohda "Analysis of the interaction mode between hyperthermophilic archaeal group II chaperonin and prefoldin using a platform of chaperonin oligomers of various subunit arrangements" Biochimica et Biophysica Acta - Proteins & Proteomics, 1804, 1810-1816 (2010)

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Muhamad Sahlan, Tamotsu Zako, Phan The Tai, Akashi Ohtaki, Keiichi Noguchi, Mizuo Maeda, Hideyuki Miyatake, Naoshi Dohmae and Masafumi Yohda "Thermodynamic Characterization of the Interaction between Prefoldin and Group II Chaperonin" J Mol. Biol. 399, 628-636 (2010)

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Zako, T., Hyodo, H., Tsuji, K., Tokuzen, K., Kishimoto, H., Ito, M., Kaneko, K., Maeda, M. and Soga, K."Development of Near Infrared-Fluorescent Nanophosphors and Applications for Cancer Diagnosis and Therapy" J. Nanomaterials, 2010, 491471 (2010)

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Bando, K., Zako, T., Sakono, M., Maeda, M., Wada, T., Nishijima, M., Fukuhara, G., Yang, C., Mori, T., Pace, T.C.S., Bohne, C. and Inoue, Y. "Bio-Supramolecular Photochirogenesis with Molecular Chaperone: Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate Mediated by Prefoldin" Photochem. Photobiol. Sci., 9, 655 - 660 (2010)

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Sakono, M. and Zako, T. "Amyloid oligomers: Formation and toxicity of Abeta oligomers" FEBS J. 277, 1348-1358(2010)

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Zako, T. "Amyloid oligomers" FEBS J. 277, 1347 (2010)

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Zako, T., Banba, S., Sahlan, M., Sakono, M., Terada, N., Yohda, M. and Maeda, M. "Hyperthermophilic archaeal prefoldin shows refolding activity at low temperature" Biochem. Biophys. Res. Commun. 391, 467-470 (2010)

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Zako, T., Sakono, M., Hashimoto, N., Ihara, M. and Maeda, M. "Bovine Insulin Filaments Induced by Reducing Disulfide Bonds Show a Different Morphology, Secondary Structure and Cell Toxicity from Intact Insulin Amyloid Fibrils" Biophys. J., 96, 3331-3340 (2009)

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Zako, T.,  Nagata, H.,  Terada, N., Utsumi, A., Sakono, M., Yohda, M., Ueda, H., Soga, K. and Maeda, M. "Cyclic RGD Peptide-Labeled Upconversion Nanophosphors for Tumor Cell-Targeted Imaging"  Biochem. Biophys. Res. Commun., 381, 54-58 (2009)

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Sakono, M., Zako, T., Ueda, H., Youda, M. and Mizuo, M. “Formation of highly toxic soluble amyloid beta oligomers by the molecular chaperone prefoldin” FEBS Journal, 275, 5982-5993 (2008)

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Zako, T., Iizuka, R., Kanzaki, T., Maeda, M. and Yohda, M. “Chaperonin and prefoldin - Two molecular chaperones that work cooperatively in archaea and eukaryote” in Heat shock proteins :New Research (Edited by Emma Moreland and Camille Vincent); pp. 393-416 Nova Science Publishers, Inc., New York, USA (2008)

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Suzuki M, Ueno T, Iizuka R, Miura T, Zako T, Akahori R, Miyake T, Shimamoto N, Aoki M, Tanii T, Ohdomari I, Funatsu T, “Effect of the C-terminal truncation on the functional cycle of chaperonin groel: Implicatoin that the C-terminal region facilitates the trasition from the folding-arrested to the folding-competent state”  J. Biol. Chem., 283, 23931-23939 (2008)

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Zako, T., Nagata, H., Terada, N., Sakono, M, Soga, K and Maeda, M. ”Improvement of dispersion stability and characterization of upconversion nanophosphors covalently modified with PEG as a fluorescence bioimaging probe” J. Materials Sci. 43, 5325-5330, (2008)

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Kurimoto E, Nishi Y, Yamaguchi Y, Zako T, Iizuka R, Ide N, Yohda M, Kato K. ”Dynamics of group II chaperonin and prefoldin probed by (13)C NMR spectroscopy.” Proteins, 70, 4, 1257-1263 (2008)

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Miyake, T, Tanii, T., Kato, K., Zako, T., Funatsu, T. and Ohdomari I. “Selectivity improvement in protein nanopatterning with a hydroxy-terminated self-assembled monolayer template” Nanotechnology, 18, 305304 (2007)

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Horiuchi, H., Iwami, N., Tachibana, F., Ohtaki, A., Iizuka, R., Zako, T., Oda, M., Yohda, M. and Tani, T. "Complex formation of CdSe/ZnS/TOPO nanocrystal vs. molecular chaperone in aqueous solution by hydrophobic interaction" J. Luminescence, 127, 192-197 (2007)

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Zako T, Murase Y, Lizuka R, Yoshida T, Kanzaki T, Ide N, Maeda M, Funatsu T, Yohda M,

“Localization of Prefoldin Interaction Sites in the Hyperthermophilic Group II  Chaperonin and Correlations between Binding Rate and Protein Transfer Rate”, J. Mol. Biol., 364, 110-120 (2006)

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Yoshida T, Kanzaki T, Iizuka R, Komada T, Zako T, Suzuki R, Maruyama T, Yohda M,

“Contribution of The C-terminal region to the thermostability of the group II  chaperonin from the hyperthermophilic archaeum, Thermococcus sp. strain KS-1”, Extremophiles, 5,  451-459 (2006)

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Terada N, Tadakuma H, Ishihama Y, Yamagihsi M, Zako T, Funatsu T,

“Analysis of Nuclear Microenvironments by Translational Diffusion of GFP Using Fluorescence Correlation Spectroscopy”, Bioimages, 13, 1-10 (2005)

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Iizuka R, Yoshida T, Ishii N, Zako T, Takahashi K, Maki K, Inobe T, Kuwajima K, Yohda M. “Characterization of Archaeal Group II Chaperonin-ADP-Metal Fluoride Complexes: IMPLICATIONS THAT GROUP II CHAPERONINS OPERATE AS A "TWO-STROKE ENGINE".” J Biol Chem. 280, 40375-83 (2005).

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Hirose M., Tohda H., Giga-Hama Y., Tsushima R., Zako T., Iizuka R., Pack C., Kinjo M., Ishii N., Yohda M.“Interaction of a Small Heat Shock Protein of the Fission Yeast, Schizosaccharomyces pombe, with a Denatured Protein at Elevated Temperature.”J Biol Chem. 280, 32586-93 (2005).

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Ayabe K., Zako T., Ueda H. ”The role of firefly luciferase C-terminal domain in efficient coupling of adenylation and oxidative steps.”, FEBS Lett. 579, 4389-94 (2005).

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Zhang G-J., Tanii T., Zako T., Hosaka T., Miyake T., Kanari Y., Funatsu T., Ohdomari I.: “Nanoscale patterning of protein using electron beam lithography of organosilane self-assembled monolayers” Small 1, 833-837 (2005).

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Zako T., Iizuka R., Okochi M., Nomura T., Ueno T., Tadakuma H., Yohda M. and Funatsu T.: “Facilitated release of substrate protein from prefoldin by chaperonin” FEBS Letters 579, 3718-3724 (2005).

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Zako T., Funatsu T. and Yohda M.: "Kinetic analysis of interactions between archaeal prefoldin and chaperonin" Recent Research Development in Biophysics, 3, 475-483 (2004).

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Okochi M., Nomura T., Zako T., Arakawa T., Iizuka R., Ueda H., Funatsu T., Leroux M., Yohda M."Kinetics and binding site for interaction of prefoldin with groupII chaperonin: contiguous non-native substrate and chaperonin binding sites in archaeal prefoldin" J Biol Chem. 279, 31788-31795 (2004).

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Yoshida, T., K. Usui, R. Iizuka, T. Zako, and M. Yohda. "Reaction mechanism of archaeal molecular chaperones" Tanpakushitsu Kakusan Koso 49, 858-61 (2004).

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Iizuka R., So S., Inobe T., Yoshida T., Zako T., Kuwajima K., Yohda M. "Role of the helical protrusion in the conformational change and molecular chaperone activity of the archaeal group II chaperonin." J Biol Chem. 279, 18834-18839 (2004).


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