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RIKEN Center for Biosystems Dynamics Research Laboratory for Dynamic Structure of Biomolecules

Team Leader: Ichio Shimada (Ph.D.)

Research Summary

Ichio Shimada (Ph.D.)

Membrane proteins play fundamental roles in many biological processes, and are recognized as principal target proteins for drug development. Over the past decade, our structural understanding of the membrane proteins has dramatically progressed, owing to the growing numbers of their atomic resolution crystal and cryo-EM structures. However, these structures basically represent static snapshots and observed conformations may not be the same as those in in-situ environment. In this research team, by using NMR, which provides us information about dynamical protein structures in solution, we will investigate the relationships between the dynamical structures and the functions for biologically important membrane proteins.

Main Research Fields

  • Medicine, Dentistry & Pharmacy

Related Research Fields

  • Biological Sciences
  • Biology
  • Physical pharmacy
  • Structural biochemistry
  • Biophysics

Keywords

  • Nuclear Magnetic Resonance
  • Biomolecules
  • Membrane Proteins
  • Dynamical Structures
  • Structural Equilibrium

Selected Publications

Papers with an asterisk(*) are based on research conducted outside of RIKEN.

  • 1. Takeuchi K, Imai M, Tokunaga Y, Fujisaki M, Kamoshida H, Takizawa T, Hanzawa H, Shimada I.:
    "Conformational plasticity of cyclic Ras-inhibitor peptides defines cell permeabilization activity"
    Angewandte Chemie International Edition (2021) doi: 10.1002/anie.202016647
  • 2. Iwahashi Y, Toyama Y, Imai S, Itoh H, Osawa M, Inoue M, Shimada I.:
    "Conformational equilibrium shift underlies altered K+ channel gating as revealed by NMR"
    Nature Communications 11, 5168 (2020) doi: 10.1038/s41467-020-19005-3
  • 3. Mizukoshi Y, Takeuchi K, Tokunaga Y, Matsuo H, Imai M, Fujisaki M, Kamoshida H, Takizawa T, Hanzawa H, Shimada I.:
    "Targeting the cryptic sites: NMR-based strategy to improve protein druggability by controlling the conformational equilibrium"
    Science Advances 6(40), eabd0480 (2020) doi: 10.1126/sciadv.abd0480
  • 4. Zhao Q, Fujimiya R, Kubo S, Marshall CB, Ikura M, Shimada I, Nishida N.:
    "Real-Time In-Cell NMR Reveals the Intracellular Modulation of GTP-Bound Levels of RAS"
    Cell Reports 32(8), 108074 (2020) doi: 10.1016/j.celrep.2020.108074
  • 5. * Mizumura T, Kondo K, Kurita M, Kofuku Y, Natsume M, Imai S, Shiraishi Y, Ueda T, and Shimada I*.:
    "Activation of adenosine A2A receptor by lipids from docosahexaenoic acid revealed by NMR"
    Sci. Adv. (2020) doi: 10.1126/sciadv.eaay8544
  • 6. * Imai S, Yokomizo T, Kofuku Y, Shiraishi Y, Ueda T, and Shimada I*.:
    "Structural equilibrium underlying ligand -dependent activation of β2 -adreno receptor."
    Nat. Chem. Bio. (2020) doi: 10.1038/s41589-019-0457-5.
  • 7. * Kano H, Toyama Y, Imai S, Iwahashi Y, Mase Y, Yokogawa M, Osawa M, and Shimada I*.:
    "Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel"
    Nat. Commun. 10(1),2008. (2019)
  • 8. * Shimada I*, Ueda T, Kofuku Y, Matthew T. Eddy, and Kurt Wuthrich*.:
    "GPCR drug discovery: integrating solution NMR data with crystal and cryo-EM structures."
    Nat. Rev. Drug Discov. 18(1), 59-82 (2019)
  • 9. * Shiraishi Y, Natsume M, Kofuku Y, Imai S, Nakata K, Mizukoshi T, Ueda T, Iwai H, and Shimada I*.:
    "Phosphorylation-induced conformation of β2-adrenoceptor related to the arrestin recruitment revealed by NMR"
    Nat. Commun. 9(1):194 (2018). doi: 10.1038/s41467-017-02632-8
  • 10. * Toyama Y, Kano H, Mase Y, Yokogawa M, Osawa M, and Shimada I*.:
    "Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses"
    Nat. Commun. 8:14523 (2017), doi: 10.1038/ncomms14523

Related Links

Lab Members

Principal investigator

Ichio Shimada
Team Leader

Core members

Shunsuke Imai
Senior Scientist
Yutaro Shiraishi
Research Scientist
Satoko Tamura
Technical Staff I

Contact Information

Central Research Building C520
1-7-22 Suehiro-cho, Tsurumi-ku
Yokohama, Kanagawa
230-0045, Japan
Email: ichio.shimada [at] riken.jp

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