Team Leader
Mikako Shirouzu Ph.D.

Laboratory for Protein Functional and Structural Biology

E-mailmikako.shirouzu[at]riken.jp

Please replace [at] with @.

Establishment of a structural analysis technology platform that contributes to "life innovation" such as drug development and medical treatment.

The high-resolution structural information of proteins related to diseases shall increasingly become important for drug development leading to future individualized medicine. We plan to establish a structural analysis technology platform to contribute to "Life innovation" such as drug discovery as well as development of methods for the sample preparation of challenging proteins including membrane proteins/biomolecular complexes and for the structural analysis by cryo-electron microscopy (cryo-EM). The 3D-structural information will be used for in-silico screening/design of chemical compounds and for dynamic structural analysis toward simulation research of cell function.

Research Theme

Analysis of developmental process using theoretical cell models
Study of evolutionary dynamics of microorganisms by comprehensive phenotypic/genetic analysis
Development of algorithm for high-resolution comprehensive phenotypic/genetic analysis

Selected Publications

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(1), 3544 (2024) doi: 10.1038/s41467-024-47792-6

Yamagata A, Ito K, Suzuki T, et al.
Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A.
Nature Communications 15(1), 3027 (2024) doi: 10.1038/s41467-024-47322-4

Akiyama N, Ishiguro K, Yokoyama T, et al.
Structural insights into the decoding capability of isoleucine tRNAs with lysidine and agmatidine.
Nature Structural & Molecular Biology (2024) doi: 10.1038/s41594-024-01238-1

Suzuki M, Uchibori K, Oh-Hara T, et al.
A macrocyclic kinase inhibitor overcomes triple resistant mutations in EGFR-positive lung cancer.
Npj Precision Oncology 8(1), 46 (2024) doi: 10.1038/s41698-024-00542-9

Tanaka M, Yokoyama T, Saito H, et al.
Boric acid intercepts 80S ribosome migration from AUG-stop by stabilizing eRF1.
Nature Chemical Biology (2024) doi: 10.1038/s41589-023-01513-0

Furutani Y, Hirano Y, Toguchi M, et al.
A small molecule iCDM-34 identified by in silico screening suppresses HBV DNA through activation of aryl hydrocarbon receptor.
Cell Death Discovery 9(1), 467 (2023) doi: 10.1038/s41420-023-01755-w

Zhao X, Ma D, Ishiguro K, et al.
Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth.
Cell 186(25), 5517-5535.e24 (2023) doi: 10.1016/j.cell.2023.10.026

Kikuchi M, Morita S, Wakamori M, et al.
Epigenetic mechanisms to propagate histone acetylation by p300/CBP.
Nature Communications 14(1), 4103 (2023) doi: 10.1038/s41467-023-39735-4

Yamagata A, Murata Y, Namba K, et al.
Uptake mechanism of iron-phytosiderophore from the soil based on the structure of yellow stripe transporter.
Nature Communications 13, 7180 (2022) doi: 10.1038/s41467-022-34930-1

Ehara H, Kujirai T, Shirouzu M, et al.
Structural basis of nucleosome disassembly and reassembly by RNAPII elongation complex with FACT.
Science 377(6611), eabp9466 (2022) doi: 10.1126/science.abp9466

Nakamura H, Hisano T, Rahman MM, et al.
Structural basis for heme detoxification by an ATP-binding cassette-type efflux pump in gram-positive pathogenic bacteria.
Proceedings of the National Academy of Sciences of the United States of America 119(27), e2123385119 (2022) doi: 10.1073/pnas.2123385119

Park JH, Iwamoto M, Yun JH, et al.
Structural insights into the HBV receptor and bile acid transporter NTCP.
Nature 606(7916), 1027-1031 (2022) doi: 10.1038/s41586-022-04857-0

Hosaka T, Nomura T, Kubo M, et al.
Conformational alterations in unidirectional ion transport of a light-driven chloride pump revealed using X-ray free electron lasers.
Proceedings of the National Academy of Sciences of the United States of America 119(9), e2117433119 (2022) doi: 10.1073/pnas.2117433119

Nakagawa Y, Shen HC, Komi Y, et al.
Amyloid conformation-dependent disaggregation in a reconstituted yeast prion system.
Nature Chemical Biology 18(3), 321-331 (2022) doi: 10.1038/s41589-021-00951-y

Kasahara K, Re S, Nawrocki G, et al.
Reduced Efficacy of a Src Kinase Inhibitor in Crowded Protein Solution.
Nature Communications 12, 4099 (2021) doi: 10.1038/s41467-021-24349-5

Kukimoto-Niino M, Katsura K, Kaushik R, et al.
Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex.
Science Advances 7(30), eabg3147 (2021) doi: 10.1126/sciadv.abg3147