Team Director
Ichio Shimada Ph.D.

Laboratory for Dynamic Structure of Biomolecules

[Affiliation has changed to RIKEN Center for Integrated Medical Sciences (IMS) as of April 2025]

E-mailichio.shimada@riken.jp

Overview
Selected Publications
Members
News

Understanding structural basis for the function of biomolecules from dynamic structures

Membrane proteins play fundamental roles in many biological processes, and are recognized as principal target proteins for drug development. RNAs have become recognized asa novel remedy to solve the depletion of targets in drug development.Over the past decade, our structural understanding of biomolecules such as the membrane proteins and RNAshas 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 structures of biomolecules in solution, we will investigate the relationships between the dynamical structures and the functions for biologically important biomolecules.

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

Selected Publications

Toyama Y, Shimada I.
Quantitative analysis of the slow exchange process by ¹⁹F NMR in the presence of scalar and dipolar couplings: applications to the ribose 2'-¹⁹F probe in nucleic acids.
Journal of Biomolecular NMR 78(4), 215-235 (2024) doi: 10.1007/s10858-024-00446-7

Kaneko S, Imai S, Uchikubo-Kamo T, et al.
Structural and dynamic insights into the activation of the μ-opioid receptor by an allosteric modulator.
Nature Communications 15, 3544 (2024) doi: 10.1038/s41467-024-47792-6

Toyama Y, Shimada I.
NMR characterization of RNA binding property of the DEAD-box RNA helicase DDX3X and its implications for helicase activity.
Nature Communications 15, 3303 (2024) doi: 10.1038/s41467-024-47659-w

Imai S, Suzuki H, Fujiyoshi Y, et al.
Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor.
Nature Communications 14, 4977 (2023) doi: 10.1038/s41467-023-40582-6

Shiraishi Y, Shimada I.
NMR Characterization of the Papain-like Protease from SARS-CoV-2 Identifies the Conformational Heterogeneity in Its Inhibitor-Binding Site.
Journal of the American Chemical Society 145, 16669-16677 (2023) doi: 10.1021/jacs.3c04115

Kaneko S, Imai S, Asao N, et al.
Activation mechanism of the μ-opioid receptor by an allosteric modulator.
Proceedings of the National Academy of Sciences 119(16), e2121918119 (2022) doi: 10.1073/pnas.2121918119

Shiraishi Y, Kofuku Y, Ueda T, et al.
Biphasic activation of β-arrestin 1 upon interaction with a GPCR revealed by methyl-TROSY NMR
Nature Communications 12, 7158 (2021) doi: 10.1038/s41467-021-27482-3

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

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

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