GoKawiilWe thank R. Danev and M. Kikkawa (UTokyo) for setting up the cryo-EM infrastructure; T. Kusakizako and Y. Sakamaki (UTokyo) and R. N. Burton-Smith and K. Murata (NIPS) for assistance with cryo-EM data collection; K. Hasegawa and A. Ohira (UTokyo) for administrative support; K. Sato, S. Nakano and Ayumi Inoue (Tohoku University) for assistance with cell-based GPCR assays; D. Mukai (Kanazawa University) for technical assistance with HS-AFM; and J. Janetzko (University of Colorado) for helpful discussions. MD simulations were partially performed using computational resources at the Center for Computational Sciences, University of Tsukuba, and the Information Technology Center, The University of Tokyo. We also acknowledge ChatGPT, a multimodal large language model created by OpenAI, for providing guidance to improve the readability of this manuscript. Note that, after using this tool, we reviewed and edited the content as needed and take full responsibility for the content of the publication. The electron microscopic observations were supported by Research Support Project for Life Science and Drug Discovery (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from the Japan Agency for Medical Research and Development (AMED) under grant numbers JP22ama121002, JP23ama121002, JP24ama121002, JP25ama121002 and JP25ama121005. Calculations were partly conducted on a supercomputer at the Research Center for Computational Science in Okazaki, Japan (project: 25-IMS-C097 to T.S.). This work was supported by JSPS KAKENHI grants (JP24K18060/JP25H02243 to K. Kobayashi, JP23KJ0363/JP24K18286/JP25H01338 to K. Kawakami, JP22K21351/JP23KJ1997 to S.Y., JP24H02262/JP25K09525 to M.F., JP24K01308 to T.S., JP23K23187 to A.S., JP20H03230 to A.M., JP21H04791/JP24K21281/JP25H01016 to A.I., JP19H03163/JP22H00400/JP25H01338 to H.E.K.); AMED grant (JP223fa627001 to K. Kobayashi, JP21zf0127005 to S.Y., JP22ama121038/JP22zf0127007 to A.I., 24bm1123057h0001 to H.E.K.); JST PRESTO (JPMJPR24OF to M.F.), JST FOREST (JPMJFP224T to A.S., JPMJFR215T to A.I., JPMJFR204S to H.E.K.), JST Moonshot (JPMJMS2023 to A.I.) and JST CREST (JPMJCR21P3/JPMJCR23B1 to H.E.K.); the Astellas Foundation for Research on Metabolic Disorders (K. Kobayashi); the Kazato Research Foundation (K. Kobayashi); The Senri Life Science Foundation (K. Kawakami); The Naito Foundation (K. Kawakami); the Hirose Foundation (K. Kawakami); The Uehara Memorial Foundation (K. Kawakami and A.I.); The Asahi Glass Foundation (H.E.K.); and the Takeda Science Foundation (H.E.K.).
The dynamic basis of G-protein recognition and activation by a GPCR
Why This Matters
This research advances our understanding of how G-protein-coupled receptors (GPCRs) recognize and activate G-proteins, which is crucial for drug development targeting these receptors. By elucidating the dynamic mechanisms involved, it opens new avenues for designing more effective therapeutics and enhances our comprehension of cellular signaling processes. The findings are significant for both the tech industry involved in structural biology and consumers benefiting from improved medical treatments.
Key Takeaways
- Provides detailed insights into GPCR-G-protein interactions
- Utilizes advanced cryo-EM and computational techniques
- Lays groundwork for targeted drug development
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