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-Structure paper
| タイトル | Cryo-EM structure of a cell-free synthesized full-length human β1-adrenergic receptor in complex with G. |
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| ジャーナル・号・ページ | Structure, Vol. 33, Issue 11, Page 1867-11877.e5, Year 2025 |
| 掲載日 | 2025年11月6日 |
著者 | Felipe Merino / Zoe Köck / Utz Ermel / Philipp Dahlhaus / Anna Grimm / Anja Seybert / Jan Kubicek / Achilleas S Frangakis / Volker Dötsch / Daniel Hilger / Frank Bernhard / ![]() |
| PubMed 要旨 | The third intracellular loop (ICL3) of the β1-adrenergic receptor (β1AR) plays a critical role in regulating G protein coupling, yet the structural basis has remained unclear due to truncations of ...The third intracellular loop (ICL3) of the β1-adrenergic receptor (β1AR) plays a critical role in regulating G protein coupling, yet the structural basis has remained unclear due to truncations of ICL3 in all available structures of the β1AR in complex with G or a G protein mimetic nanobody. To address this, we used cell-free cotranslational insertion of full-length human β1AR into nanodiscs and determined its cryo-electron microscopy (cryo-EM) structure in complex with G. In this structure, ICL3 extends transmembrane helix 5, resulting in enhanced interactions with Gα and in a slight rotation of the engaged G protein. This repositioning enables new polar interactions between Gα, ICL2 and helix 8, while ICL1 and helix 8 form additional contacts with Gβ. These structural insights, supported by mutational analysis, demonstrate that ICL3 enhances G protein activation and downstream cAMP signaling by promoting more extensive interactions between the receptor and the heterotrimeric G protein. |
リンク | Structure / PubMed:40858117 |
| 手法 | EM (単粒子) |
| 解像度 | 3.3 Å |
| 構造データ | EMDB-19683, PDB-8s2t: |
| 化合物 | ![]() ChemComp-5FW: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / Signal transduction / GPCR / co-translational nanodisc insertion / G-protein |
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