シグナル探求学講座

2025 年度

49. Tanaka, Y.; Osakabe, A.; Shihoya, W.; Hirano, H.; Itoh, Y.; Kakutani, T.; Nureki, O. Structure and Evolution of the Sequence-Specific Anti-Silencing Factor VANC21 and Its Target DNA. Genes & Genetic Systems 2026, 101. 10.1266/ggs.25-00096.
50. Fu, J.; Kamiya, K.; Kitamura, K.; Kawahara, R.; Shihoya, W.; Nureki, O.; Hosoya, S.; Nakagawa, R.; Mashima, T.; Itoh, H.; Inoue, M.; Sakurai, K. Photoaffinity Labeling Strategy Reveals Tetraspanin CD9 as a Transient Target of Anticancer Yaku’amide B. J. Am. Chem. Soc. 2026, 148 (3), 2985–2994. 10.1021/jacs.5c13808.
51. Marín, M. del C.; Murakoshi, S.; Rozenberg, A.; Tanaka, T.; Konno, M.; Shihoya, W.; Nureki, O.; Béjà, O.; Inoue, K. Light-Harvesting by Antenna-Containing Xanthorhodopsin from an Antarctic Pseudanabaenaceae Cyanobacterium. Commun Biol 2025, 9 (1), 28. 10.1038/s42003-025-09294-z.
52. Kosugi, Y.; Matsumoto, K.; Lytras, S.; Plianchaisuk, A.; Tolentino, J. E.; Fujita, S.; Yo, M. S.; Luo, C.; Kim, Y.; Shihoya, W.; Ito, J.; Nureki, O.; Sato, K. Molecular Basis of Sarbecovirus Evolution and Receptor Tropism in Natural Hosts, Potential Intermediate Hosts, and Humans. Cell Reports 2025, 44 (9), 116220. 10.1016/j.celrep.2025.116220.
53. Matsuzaki, Y.; Sano, F. K.; Oshima, H. S.; Akasaka, H.; Kobayashi, K.; Tanaka, T.; Itoh, Y.; Shihoya, W.; Kise, Y.; Kusakizako, T.; Inoue, A.; Nureki, O. Structural Insights into Ligand Recognition and G Protein Preferences across Histamine Receptors. Commun Biol 2025, 8 (1), 957. 10.1038/s42003-025-08363-7.
54. Sano, F. K.; Shimizume, K.; Kobayashi, K.; Awazu, T.; Kawakami, K.; Akasaka, H.; Kobayashi, T. A.; Tanaka, T.; Okamoto, H. H.; Hirano, H.; Kusakizako, T.; Shihoya, W.; Kise, Y.; Itoh, Y.; Ishitani, R.; Okada, Y.; Sako, Y.; Yanagawa, M.; Inoue, A.; Nureki, O. Insights into G-Protein Coupling Preference from Cryo-EM Structures of Gq-Bound PTH1R. Nat Chem Biol 2025, 1–9. 10.1038/s41589-025-01957-6.
55. Wang, Y. Z.; Natsume, K.; Tanaka, T.; Hososhima, S.; Tashiro, R.; Sano, F. K.; Akasaka, H.; Tsunoda, S. P.; Shihoya, W.; Kandori, H.; Nureki, O. Cryo-EM Structure of a Blue-Shifted Channelrhodopsin from Klebsormidium Nitens. Nat Commun 2025, 16 (1), 5297. 10.1038/s41467-025-59299-9.
56. Tzlil, G.; Marín, M. del C.; Matsuzaki, Y.; Nag, P.; Itakura, S.; Mizuno, Y.; Murakoshi, S.; Tanaka, T.; Larom, S.; Konno, M.; Abe-Yoshizumi, R.; Molina-Márquez, A.; Bárcenas-Pérez, D.; Cheel, J.; Koblížek, M.; León, R.; Katayama, K.; Kandori, H.; Schapiro, I.; Shihoya, W.; Nureki, O.; Inoue, K.; Rozenberg, A.; Chazan, A.; Béjà, O. Structural Insights into Light Harvesting by Antenna-Containing Rhodopsins in Marine Asgard Archaea. Nat Microbiol 2025, 10 (6), 1484–1500. 10.1038/s41564-025-02016-5.
57. Shihoya, W.; Akasaka, H.; Jordan, P. A.; Lechner, A.; Okada, B. K.; Costa Machado da Cruz, G.; Sano, F. K.; Tanaka, T.; Kawahara, R.; Chaudhari, R.; Masamune, H.; Burk, M. J.; Nureki, O. Structure of a Lasso Peptide Bound ETB Receptor Provides Insights into the Mechanism of GPCR Inverse Agonism. Nat Commun 2025, 16 (1), 3446. 10.1038/s41467-025-57960-x.

2024 年度

40. Saha, S.; Sano, F. K.; Sharma, S.; Ganguly, M.; Dalal, A.; Mishra, S.; Tiwari, D.; Akasaka, H.; Kobayashi, T. A.; Roy, N.; Zaidi, N.; Itoh, Y.; Leurs, R.; Banerjee, R.; Shihoya, W.; Nureki, O.; Shukla, A. K. Structural Visualization of Small Molecule Recognition by CXCR3 Uncovers Dual-Agonism in the CXCR3-CXCR7 System. Nat Commun 2025, 16 (1), 3047. 10.1038/s41467-025-58264-w.
41. Saha, S.; Sano, F. K.; Sharma, S.; Ganguly, M.; Mishra, S.; Dalal, A.; Akasaka, H.; Kobayashi, T. A.; Zaidi, N.; Tiwari, D.; Roy, N.; Yadav, M. K.; Banerjee, N.; Saha, S.; Mohapatra, S.; Itoh, Y.; Chevigné, A.; Banerjee, R.; Shihoya, W.; Nureki, O.; Shukla, A. K. Molecular Basis of Promiscuous Chemokine Binding and Structural Mimicry at the C-X-C Chemokine Receptor, CXCR2. Molecular Cell 2025, 85 (5), 976-988.e9. 10.1016/j.molcel.2025.01.024.
42. Oshima, H. S.; Ogawa, A.; Sano, F. K.; Akasaka, H.; Kawakami, T.; Iwama, A.; Okamoto, H. H.; Nagiri, C.; Wei, F.-Y.; Shihoya, W.; Nureki, O. Structural Insights into the Agonist Selectivity of the Adenosine A3 Receptor. Nat Commun 2024, 15 (1), 9294. 10.1038/s41467-024-53473-1.
43. Akasaka, H.; Sano, F. K.; Shihoya, W.; Nureki, O. Structural Mechanisms of Potent Lysophosphatidic Acid Receptor 1 Activation by Nonlipid Basic Agonists. Commun Biol 2024, 7 (1), 1444. 10.1038/s42003-024-07152-y.
44. Ham, D.; Shihoya, W.; Nureki, O.; Inoue, A.; Chung, K. Y. Molecular Mechanism of the Endothelin Receptor Type B Interactions with Gs, Gi, and Gq. Structure 2024, 32 (10), 1632-1639.e4. 10.1016/j.str.2024.06.020.
45. Tanaka, T.; Hososhima, S.; Yamashita, Y.; Sugimoto, T.; Nakamura, T.; Shigemura, S.; Iida, W.; Sano, F. K.; Oda, K.; Uchihashi, T.; Katayama, K.; Furutani, Y.; Tsunoda, S. P.; Shihoya, W.; Kandori, H.; Nureki, O. The High-Light-Sensitivity Mechanism and Optogenetic Properties of the Bacteriorhodopsin-like Channelrhodopsin GtCCR4. Molecular Cell 2024, 84 (18), 3530-3544.e6. 10.1016/j.molcel.2024.08.016.
46. Akasaka, H.; Sato, D.; Shihoya, W.; Nureki, O.; Kise, Y. Cryo-EM Structure of I Domain-Containing Integrin αEβ7. Biochemical and Biophysical Research Communications 2024, 721, 150121. 10.1016/j.bbrc.2024.150121.
47. Shihoya, W.; Iwama, A.; Sano, F. K.; Nureki, O. Cryo-EM Advances in GPCR Structure Determination. J Biochem 2024, 176 (1), 1–10. 10.1093/jb/mvae029.
48. Iwama, A.; Kise, R.; Akasaka, H.; Sano, F. K.; Oshima, H. S.; Inoue, A.; Shihoya, W.; Nureki, O. Structure and Dynamics of the Pyroglutamylated RF-Amide Peptide QRFP Receptor GPR103. Nat Commun 2024, 15 (1), 4769. 10.1038/s41467-024-49030-5.

2023 年度

31. Izume, T.; Kawahara, R.; Uwamizu, A.; Chen, L.; Yaginuma, S.; Omi, J.; Kawana, H.; Hou, F.; Sano, F. K.; Tanaka, T.; Kobayashi, K.; Okamoto, H. H.; Kise, Y.; Ohwada, T.; Aoki, J.; Shihoya, W.; Nureki, O. Structural Basis for Lysophosphatidylserine Recognition by GPR34. Nat Commun 2024, 15 (1), 902. 10.1038/s41467-024-45046-z.
32. Oshima, H. S.; Sano, F. K.; Akasaka, H.; Iwama, A.; Shihoya, W.; Nureki, O. Optimizing Cryo-EM Structural Analysis of Gi-Coupling Receptors via Engineered Gt and Nb35 Application. Biochemical and Biophysical Research Communications 2024, 693, 149361. 10.1016/j.bbrc.2023.149361.
33. Maharana, J.; Sano, F. K.; Sarma, P.; Yadav, M. K.; Duan, L.; Stepniewski, T. M.; Chaturvedi, M.; Ranjan, A.; Singh, V.; Saha, S.; Mahajan, G.; Chami, M.; Shihoya, W.; Selent, J.; Chung, K. Y.; Banerjee, R.; Nureki, O.; Shukla, A. K. Molecular Insights into Atypical Modes of β-Arrestin Interaction with Seven Transmembrane Receptors. Science 2024, 383 (6678), 101–108. 10.1126/science.adj3347.
34. Shihoya, W.; Sano, F. K.; Nureki, O. Structural Insights into Endothelin Receptor Signalling. J Biochem 2023, 174 (4), 317–325. 10.1093/jb/mvad055.
35. Sano, F. K.; Akasaka, H.; Shihoya, W.; Nureki, O. Cryo-EM Structure of the Endothelin-1-ETB-Gi Complex. eLife 2023, 12, e85821. 10.7554/eLife.85821.

2022 年度

26. Chazan, A.; Das, I.; Fujiwara, T.; Murakoshi, S.; Rozenberg, A.; Molina-Márquez, A.; Sano, F. K.; Tanaka, T.; Gómez-Villegas, P.; Larom, S.; Pushkarev, A.; Malakar, P.; Hasegawa, M.; Tsukamoto, Y.; Ishizuka, T.; Konno, M.; Nagata, T.; Mizuno, Y.; Katayama, K.; Abe-Yoshizumi, R.; Ruhman, S.; Inoue, K.; Kandori, H.; León, R.; Shihoya, W.; Yoshizawa, S.; Sheves, M.; Nureki, O.; Béjà, O. Phototrophy by Antenna-Containing Rhodopsin Pumps in Aquatic Environments. Nature 2023, 615 (7952), 535–540. 10.1038/s41586-023-05774-6.
27. Kobayashi, K.; Kawakami, K.; Kusakizako, T.; Miyauchi, H.; Tomita, A.; Kobayashi, K.; Shihoya, W.; Yamashita, K.; Nishizawa, T.; Kato, H. E.; Inoue, A.; Nureki, O. Endogenous Ligand Recognition and Structural Transition of a Human PTH Receptor. Molecular Cell 2022, 82 (18), 3468-3483.e5. 10.1016/j.molcel.2022.07.003.
28. Akasaka, H.; Tanaka, T.; Sano, F. K.; Matsuzaki, Y.; Shihoya, W.; Nureki, O. Structure of the Active Gi-Coupled Human Lysophosphatidic Acid Receptor 1 Complexed with a Potent Agonist. Nat Commun 2022, 13 (1), 5417. 10.1038/s41467-022-33121-2.
29. Nureki, I.; Kobayashi, K.; Tanaka, T.; Demura, K.; Inoue, A.; Shihoya, W.; Nureki, O. Cryo-EM Structures of the Β3 Adrenergic Receptor Bound to Solabegron and Isoproterenol. Biochemical and Biophysical Research Communications 2022, 611, 158–164. 10.1016/j.bbrc.2022.04.065.
30. Ujiantari, N. S. O.; Ham, S.; Nagiri, C.; Shihoya, W.; Nureki, O.; Hutchinson, D. S.; Schuster, D. Pharmacophore-Guided Virtual Screening to Identify New Β3-Adrenergic Receptor Agonists. Molecular Informatics 2022, 41 (7), 2100223. 10.1002/minf.202100223.

2021 年度

21. Nakai, H.; Isshiki, K.; Hattori, M.; Maehira, H.; Yamaguchi, T.; Masuda, K.; Shimizu, Y.; Watanabe, T.; Hohsaka, T.; Shihoya, W.; Nureki, O.; Kato, Y.; Watanabe, H.; Matsuura, T. Cell-Free Synthesis of Human Endothelin Receptors and Its Application to Ribosome Display. Anal. Chem. 2022, 94 (9), 3831–3839. 10.1021/acs.analchem.1c04714.
22. Nagiri, C.; Kobayashi, K.; Tomita, A.; Kato, M.; Kobayashi, K.; Yamashita, K.; Nishizawa, T.; Inoue, A.; Shihoya, W.; Nureki, O. Cryo-EM Structure of the Β3-Adrenergic Receptor Reveals the Molecular Basis of Subtype Selectivity. Molecular Cell 2021, 81 (15), 3205-3215.e5. 10.1016/j.molcel.2021.06.024.
23. Okamoto, H. H.; Miyauchi, H.; Inoue, A.; Raimondi, F.; Tsujimoto, H.; Kusakizako, T.; Shihoya, W.; Yamashita, K.; Suno, R.; Nomura, N.; Kobayashi, T.; Iwata, S.; Nishizawa, T.; Nureki, O. Cryo-EM Structure of the Human MT1–Gi Signaling Complex. Nat Struct Mol Biol 2021, 28 (8), 694–701. 10.1038/s41594-021-00634-1.
24. Higuchi, A.; Shihoya, W.; Konno, M.; Ikuta, T.; Kandori, H.; Inoue, K.; Nureki, O. Crystal Structure of Schizorhodopsin Reveals Mechanism of Inward Proton Pumping. PNAS 2021, 118 (14). 10.1073/pnas.2016328118.

2020 年度

17. Oda, K.; Nomura, T.; Nakane, T.; Yamashita, K.; Inoue, K.; Ito, S.; Vierock, J.; Hirata, K.; Maturana, A. D.; Katayama, K.; Ikuta, T.; Ishigami, I.; Izume, T.; Umeda, R.; Eguma, R.; Oishi, S.; Kasuya, G.; Kato, T.; Kusakizako, T.; Shihoya, W.; Shimada, H.; Takatsuji, T.; Takemoto, M.; Taniguchi, R.; Tomita, A.; Nakamura, R.; Fukuda, M.; Miyauchi, H.; Lee, Y.; Nango, E.; Tanaka, R.; Tanaka, T.; Sugahara, M.; Kimura, T.; Shimamura, T.; Fujiwara, T.; Yamanaka, Y.; Owada, S.; Joti, Y.; Tono, K.; Ishitani, R.; Hayashi, S.; Kandori, H.; Hegemann, P.; Iwata, S.; Kubo, M.; Nishizawa, T.; Nureki, O. Time-Resolved Serial Femtosecond Crystallography Reveals Early Structural Changes in Channelrhodopsin. eLife 2021, 10, e62389. 10.7554/eLife.62389.
18. Ogawa, A.; Nagiri, C.; Shihoya, W.; Inoue, A.; Kawakami, K.; Hiratsuka, S.; Aoki, J.; Ito, Y.; Suzuki, T.; Suzuki, T.; Inoue, T.; Nureki, O.; Tanihara, H.; Tomizawa, K.; Wei, F.-Y. N6-Methyladenosine (m6A) Is an Endogenous A3 Adenosine Receptor Ligand. Molecular Cell 2021, 81 (4), 659-674.e7. 10.1016/j.molcel.2020.12.038.
19. Fukuhara, S.; Kobayashi, K.; Kusakizako, T.; Iida, W.; Kato, M.; Shihoya, W.; Nureki, O. Structure of the Human Secretin Receptor Coupled to an Engineered Heterotrimeric G Protein. Biochemical and Biophysical Research Communications 2020, 533 (4), 861–866. 10.1016/j.bbrc.2020.08.042.
20. Tanaka, T.; Singh, M.; Shihoya, W.; Yamashita, K.; Kandori, H.; Nureki, O. Structural Basis for Unique Color Tuning Mechanism in Heliorhodopsin. Biochemical and Biophysical Research Communications 2020, 533 (3), 262–267. 10.1016/j.bbrc.2020.06.124.
21. Ikuta, T.; Shihoya, W.; Sugiura, M.; Yoshida, K.; Watari, M.; Tokano, T.; Yamashita, K.; Katayama, K.; Tsunoda, S. P.; Uchihashi, T.; Kandori, H.; Nureki, O. Structural Insights into the Mechanism of Rhodopsin Phosphodiesterase. Nat Commun 2020, 11 (1), 5605. 10.1038/s41467-020-19376-7.
22. Izume, T.; Miyauchi, H.; Shihoya, W.; Nureki, O. Crystal Structure of Human Endothelin ETB Receptor in Complex with Sarafotoxin S6b. Biochemical and Biophysical Research Communications 2020, 528 (2), 383–388. 10.1016/j.bbrc.2019.12.091.
23. Demura, K.; Kusakizako, T.; Shihoya, W.; Hiraizumi, M.; Nomura, K.; Shimada, H.; Yamashita, K.; Nishizawa, T.; Taruno, A.; Nureki, O. Cryo-EM Structures of Calcium Homeostasis Modulator Channels in Diverse Oligomeric Assemblies. Science Advances 2020, 6 (29), eaba8105. 10.1126/sciadv.aba8105.

2019 年度

10. Kobayashi, K.; Shihoya, W.; Nishizawa, T.; Kadji, F. M. N.; Aoki, J.; Inoue, A.; Nureki, O. Cryo-EM Structure of the Human PAC1 Receptor Coupled to an Engineered Heterotrimeric G Protein. Nat Struct Mol Biol 2020, 27 (3), 274–280. 10.1038/s41594-020-0386-8.
11. Shihoya, W.; Inoue, K.; Singh, M.; Konno, M.; Hososhima, S.; Yamashita, K.; Ikeda, K.; Higuchi, A.; Izume, T.; Okazaki, S.; Hashimoto, M.; Mizutori, R.; Tomida, S.; Yamauchi, Y.; Abe-Yoshizumi, R.; Katayama, K.; Tsunoda, S. P.; Shibata, M.; Furutani, Y.; Pushkarev, A.; Béjà, O.; Uchihashi, T.; Kandori, H.; Nureki, O. Crystal Structure of Heliorhodopsin. Nature 2019, 574 (7776), 132–136. 10.1038/s41586-019-1604-6.
12. Nagiri, C.; Shihoya, W.; Inoue, A.; Kadji, F. M. N.; Aoki, J.; Nureki, O. Crystal Structure of Human Endothelin ET B Receptor in Complex with Peptide Inverse Agonist IRL2500. Commun Biol 2019, 2 (1), 1–10. 10.1038/s42003-019-0482-7.

2018 年度

7. Tahara, S.; Singh, M.; Kuramochi, H.; Shihoya, W.; Inoue, K.; Nureki, O.; Béjà, O.; Mizutani, Y.; Kandori, H.; Tahara, T. Ultrafast Dynamics of Heliorhodopsins. J. Phys. Chem. B 2019, 123 (11), 2507–2512. 10.1021/acs.jpcb.9b00887.
8. Watari, M.; Ikuta, T.; Yamada, D.; Shihoya, W.; Yoshida, K.; Tsunoda, S. P.; Nureki, O.; Kandori, H. Spectroscopic Study of the Transmembrane Domain of a Rhodopsin–Phosphodiesterase Fusion Protein from a Unicellular Eukaryote. J. Biol. Chem. 2019, jbc.RA118.006277. 10.1074/jbc.RA118.006277.
9. Otomo, A.; Mizuno, M.; Singh, M.; Shihoya, W.; Inoue, K.; Nureki, O.; Béjà, O.; Kandori, H.; Mizutani, Y. Resonance Raman Investigation of the Chromophore Structure of Heliorhodopsins. J. Phys. Chem. Lett. 2018, 9 (22), 6431–6436. 10.1021/acs.jpclett.8b02741
10. Shihoya, W.; Izume, T.; Inoue, A.; Yamashita, K.; Kadji, F. M. N.; Hirata, K.; Aoki, J.; Nishizawa, T.; Nureki, O. Crystal Structures of Human ETB Receptor Provide Mechanistic Insight into Receptor Activation and Partial Activation. Nat Commun 2018, 9 (1), 4711. 10.1038/s41467-018-07094-0.
11. Morita, K.; Hama, Y.; Izume, T.; Tamura, N.; Ueno, T.; Yamashita, Y.; Sakamaki, Y.; Mimura, K.; Morishita, H.; Shihoya, W.; Nureki, O.; Mano, H.; Mizushima, N. Genome-Wide CRISPR Screen Identifies TMEM41B as a Gene Required for Autophagosome Formation. J Cell Biol 2018, 217 (11), 3817–3828. 10.1083/jcb.201804132.

2017 年度

2. Shihoya, W.; Nishizawa, T.; Yamashita, K.; Inoue, A.; Hirata, K.; Kadji, F. M. N.; Okuta, A.; Tani, K.; Aoki, J.; Fujiyoshi, Y.; Doi, T.; Nureki, O. X-Ray Structures of Endothelin ETB Receptor Bound to Clinical Antagonist Bosentan and Its Analog. Nat Struct Mol Biol 2017, 24 (9), 758–764. 10.1038/nsmb.3450.

2016 年度

1. Shihoya, W.; Nishizawa, T.; Okuta, A.; Tani, K.; Dohmae, N.; Fujiyoshi, Y.; Nureki, O.; Doi, T. Activation Mechanism of Endothelin ETB Receptor by Endothelin-1. Nature 2016, 537 (7620), 363–368. 10.1038/nature19319.