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Structural Biology of Protein Post-transcriptional Modifications and Cellular Signaling

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Protein Modifications in Pathogenic Dysregulation of Signaling

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Abstract

Post-translational modifications play critical roles in the regulation of signal transduction and cellular functions. Structural biology methods, including X-ray crystallography, are powerful tools for dissecting the molecular interaction mechanisms among the factors involved in these signaling pathways. Therefore, synergetic approaches by structural, molecular, and cellular biology are important to understand both the mechanisms of signal transduction by post-translational modifications and their pathogenic dysregulation. In this chapter, we introduce our recent results from structural and functional analyses of proteins involved in signal transduction by the post-transcriptional modifications. In the first section, we discuss the structural analyses of cGAS, which revealed the precise mechanism of the DNA-specific conformational activation of cGAS and cGAMP production. In the second section, we discuss the structural insights of the regulation of the NF-κB pathway by A20. In the final section, we discuss the crystal structure of a dnHLH protein, HHM, in an auto-inhibited form, which adopts a characteristic V-shaped structure. These results highlight the importance of synergetic approaches by collaborations between different biological fields.

To whom reprint requests should be addressed: Ryuichiro Ishitani: Phone: +81-3-5841-4392; Facsimile: +81-3-5841-8057; E-mail: ishitani@bs.s.u-tokyo.ac.jp

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Authors and Affiliations

  1. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Kazuki Kato, Hiroshi Nishimasu, Ryohei Ishii, Osamu Nureki & Ryuichiro Ishitani

Authors
  1. Kazuki Kato
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  2. Hiroshi Nishimasu
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  3. Ryohei Ishii
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  4. Osamu Nureki
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  5. Ryuichiro Ishitani
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Correspondence to Ryuichiro Ishitani .

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Editors and Affiliations

  1. Division of Cellular & Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Jun-ichiro Inoue

  2. The Institute of Medical Science Division of Cell Signaling & Molecular Medicine, The University of Tokyo, Tokyo, Japan

    Mutsuhiro Takekawa

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Kato, K., Nishimasu, H., Ishii, R., Nureki, O., Ishitani, R. (2015). Structural Biology of Protein Post-transcriptional Modifications and Cellular Signaling. In: Inoue, Ji., Takekawa, M. (eds) Protein Modifications in Pathogenic Dysregulation of Signaling. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55561-2_8

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