Stabilization of drug-target proteins by sulfobetaines
| Project/Area Number |
24570124
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Gunma University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
Terawaki Shin-ichi 群馬大学, 大学院理工学府, 助教 (10452533)
Iizuka Yasuko 群馬大学, 理工学部, 技術長 (60375566)
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| Research Collaborator |
Hosoda Kazuo
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 蛋白質 / 安定化 / スルホベタイン / メカニズム / ダイナミクス / GPCR / Ｇ蛋白質 / 抗体 / Ｇタンパク質 / リフォールディング / cis-trans異性化 / タンパク質 / オスモライト |
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| Outline of Final Research Achievements |
Stabilization of proteins (prevention of denaturation and aggregation) is important in drug development. Sulfobetaines are a class of protein stabilizer whose mechanisms remain elusive. To elucidate their stabilizing mechanisms, we analyzed their effects on protein dynamics. We found that NDSB-195 enhances the dynamics of β4-α2 loop of ubiquitin molecules and that NDSB-256 enhances the cis-trans isomerization of an Ala-Pro peptide bond. These effects may contribute the stabilizing activities of sulfobetaines by helping the denatured protein molecules escape from kinetic traps. In addition, by expressing proteins and peptides as fusion proteins, we succeeded in obtaining soluble complex of Gαi1 and its activator peptide designed from the junction between the intracellular third loop and sixth transmembrane helix in the m4 muscarinic acetylcholine receptor. We also identified 3 residues in the peptide that are critical for the binding with Gαi1.
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Report
(5 results)
Research Products
(31 results)
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[Journal Article] Protein stabilizer, NDSB-195, enhances the dynamics of the β4-α2 loop of ubiqutin.2016
Author(s)
Wang, H., Hosoda, K., Ishii, T., Arai, R., Kohno, T., Terawaki, S. & Wakamatsu, K.
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Journal Title
J. Pept. Sci.
Volume: 22
Issue: 3
Pages: 174-180
DOI
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Peer Reviewed / Acknowledgement Compliant
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[Presentation] Analysis of the mechanisms whereby sulfobetaines stabilize proteins2013
Author(s)
Kaori Wakamatsu, Tetsuro Demura, Ryutaro Ohtsuki, Ryo Arai, Akino Sayama, Mutsumi Wakayama, Takanori Sanai, Fukuei Tetsuka, Mitsuhiko Yoshizawa, Haimei Wang, Takeshi Ishii, Kazuo Hosoda, Yasuko Iizuka, Nobukazu Nameki
Organizer
第86回日本生化学会大会
Place of Presentation
パシフィコ横浜（神奈川県，横浜市）
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