Photocontrol of GTPase Cycle and Multimerization of the Small G-Protein H-Ras using Photochromic Azobenzene Derivatives
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Published:2021-12-30
Issue:4
Volume:18
Page:661-672
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ISSN:2456-2602
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Container-title:Biosciences Biotechnology Research Asia
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language:en
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Short-container-title:Biosci., Biotech. Res. Asia
Author:
Nahar Rufiat1ORCID, Noor A Alam MD1ORCID, Alrazi Islam MD1ORCID, Maruta Shinsaku1ORCID
Affiliation:
1. Division of Bioinformatics, Graduate School of Engineering, Soka University, Hachioji, Tokyo 192-8577, Japan
Abstract
Ras is a small G protein known as a central regulator of cellular signal transduction that induces processes, such as cell division, transcription. The hypervariable region (HVR) is one of the functional parts of this G protein, which induces multimerization and interaction between Ras and the plasma membrane. We introduced two highly different in polarity photochromic SH group-reactive azobenzene derivatives, N-4-phenyl-azophenyl maleimide (PAM) and 4-chloroacetoamido-4-sulfo-azobenzene (CASAB), into three cysteine residues in HVR to control Ras GTPase using light. PAM stoichiometrically reacted with the SH group of cysteine residues and induced multimerization. The mutants modified with PAM exhibited reversible changes in GTPase activity accelerated by the guanine nucleotide exchange factor and GTPase activating protein and multimerization accompanied by cis- and trans-photoisomerization upon ultraviolet and visible light irradiation. CASAB was incorporated into two of the three cysteine residues in HVR but did not induce multimerization. The H-Ras GTPase modified with CASAB was photo controlled more effectively than PAM-H-Ras. In this study, we revealed that the incorporation of azobenzene derivatives into the functional site of HVR enables photo reversible control of Ras function. Our findings may contribute to the development of a method to control functional biomolecules with physiologically important roles.
Publisher
Oriental Scientific Publishing Company
Subject
Drug Discovery,Agronomy and Crop Science,Biotechnology
Reference25 articles.
1. 1. Fernandez-Medarde, A., & Santos, E. (2011). Ras in cancer and developmental diseases. Genes Cancer 2: 344–358. 2. 2. Campbell, S. L., Khosravi-Far, R., Rossman, K. L., Clark, G. J., & Der, C. J. (1998). Increasing complexity of Ras signaling. Oncogene, 17(11), 1395-1413. 3. 3. Marshall, C. B., Meiri, D., Smith, M. J., Mazhab-Jafari, M. T., Gasmi-Seabrook, G. M., Rottapel, R., … & Ikura, M. (2012). Probing the GTPase cycle with real-time NMR: GAP and GEF activities in cell extracts. Methods, 57(4), 473-485. 4. 4. Kull, F. J., Vale, R. D., & Fletterick, R. J. (1998). The case for a common ancestor: kinesin and myosin motor proteins and G proteins. Journal of Muscle Research & Cell Motility, 19(8), 877-886. 5. 5. Yamada, M. D., Nakajima, Y., Maeda, H., & Maruta, S. (2007). Photocontrol of kinesin ATPase activity using an azobenzene derivative. Journal of biochemistry, 142(6), 691-698.
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