Laboratory for Dynamic Structure of Biomolecules | RIKEN BDR

Laboratory for Dynamic Structure of Biomolecules

Team Leader

Ichio ShimadaPh.D.

Photo of principal investigator

  • Location:Yokohama
  • E-mail:ichio.shimada[at]riken.jpPlease replace [at] with @.

Understanding structural basis for the function of biomolecules from dynamic structures

Research Summary

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.

Research Theme

  • Elucidation of functional mechanism of biomolecules from dynamic structures
  • Elucidation of signal transduction mechanism of GPCRs from dynamic structures
  • Development of methods for dynamic structures of membrane proteins in lipid bilayers
  • Development of NMR methods applicable to high-molecular-weight biomolecules

Main Publications List

  • Takeuchi K, Misaki I, Tokunaga Y, et al.
    Conformational plasticity of cyclic Ras-inhibitor peptides defines cell permeabilization activity.
    Angewandte Chemie International Edition (2021) doi: 10.1002/anie.202016647
  • Iwahashi Y, Toyama Y, Imai S, et al.
    Conformational equilibrium shift underlies altered K+ channel gating as revealed by NMR
    Nature Communications 11, 5168 (2020) doi: 10.1038/s41467-020-19005-3
  • Mizukoshi Y, Takeuchi K, Tokunaga Y, et al.
    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
  • Zhao Q, Fujimiya R, Kubo S, et al.
    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
  • Mizumura T, Kondo K, Kurita M, et al.
    Activation of adenosine A2A receptor by lipids from docosahexaenoic acid revealed by NMR.
    Science Advances 6(12), eaay8544 (2020) doi: 10.1126/sciadv.aay8544
  • Imai S, Yokomizo T, Kofuku Y, et al.
    Structural equilibrium underlying ligand -dependent activation of β2 -adreno receptor.
    Nature Chemical Biology 16, 430-439 (2020) doi: 10.1038/s41589-019-0457-5
  • Kano H, Toyama Y, Imai S, et al.
    Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel.
    Nature Communications 10(1), 2008 (2019) doi: 10.1038/s41467-019-10038-x
  • Shimada I, Ueda T, Kofuku Y, et al.
    GPCR drug discovery: integrating solution NMR data with crystal and cryo-EM structures.
    Nature Reviews Drug Discovery 18(1), 59-82 (2019) doi: 10.1038/nrd.2018.180
  • Shiraishi Y, Natsume M, Kofuku Y, et al.
    Phosphorylation-induced conformation of β2-adrenoceptor related to the arrestin recruitment revealed by NMR.
    Nature Communications 9(1), 194 (2018) doi: 10.1038/s41467-017-02632-8
  • Toyama Y, Kano H, Mase Y, et al.
    Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses
    Nature Communications 8, 14523 (2017) doi: 10.1038/ncomms14523
  • Tokunaga Y, Takeuchi K, Takahashi H, et al.
    Allosteric enhancement of MAP kinase p38α's activity and substrate selectivity by docking interactions.
    Nature Structural & Molecular Biology 21, 704–711 (2014) doi: 10.1038/nsmb.2861
  • Kofuku Y, Ueda T, Okude J, et al.
    Efficacy of the β2-adrenergic receptor is determined by conformational equilibrium in the transmembrane region
    Nature Communications 3, 1045 (2012) doi: 10.1038/ncomms2046
  • Nishida N, Sumikawa H, Sakakura M, et al.
    Collagen-binding mode of vWF-A3 domain determined by a transferred cross-saturation experiment.
    Nature Structural Biology 10, 53–58 (2003) doi: 10.1038/nsb876
  • Takahashi H, Nakanishi T, Kami K, et al.
    A novel NMR method for determining the interfaces of large protein–protein complexes.
    Nature Structural Biology 7, 220–223 (2000) doi: 10.1038/73331

Member

Ichio ShimadaTeam Leader ichio.shimada[at]riken.jp  
Shunsuke ImaiSenior Scientist    
Yutaro ShiraishiResearch Scientist    
Satoko TamuraTechnical Staff I    

*:concurrent / Please replace [at] with @.