チームディレクター
白水美香子 Ph.D.

タンパク質機能・構造研究チーム

[2025年4月よりBDRから生命医科学研究センター(IMS)に所属が変わりました]

E-mail mikako.shirouzu@riken.jp

創薬・医療等のライフイノベーションに貢献する構造解析技術基盤を構築

個別化医療を実現する薬の開発においては、ターゲットとなる疾患に関与するタンパク質の機能と構造の情報の蓄積が一層重要となります。これまで解析が難しかった膜タンパク質をはじめとする高難度タンパク質の試料調製法や、生体分子複合体のクライオ電子顕微鏡による解析技術の開発を進めながら、創薬・医療等のライフイノベーションに貢献する構造解析技術の基盤を構築します。立体構造情報は、候補化合物のインシリコスクリーニングや動的構造計算に供され、創薬への貢献や、細胞機能のシミュレーション研究へと発展することが期待されます。

主要論文

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