8JPE
Focused refinement structure of Galpha(q) in NTSR1-GRK2-Galpha(q) complexes
Summary for 8JPE
| Entry DOI | 10.2210/pdb8jpe/pdb |
| EMDB information | 36477 |
| Descriptor | Guanine nucleotide-binding protein G(q) subunit alpha, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | biased signaling, signaling protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 41853.38 |
| Authors | |
| Primary citation | Duan, J.,Liu, H.,Zhao, F.,Yuan, Q.,Ji, Y.,Cai, X.,He, X.,Li, X.,Li, J.,Wu, K.,Gao, T.,Zhu, S.,Lin, S.,Wang, M.W.,Cheng, X.,Yin, W.,Jiang, Y.,Yang, D.,Xu, H.E. GPCR activation and GRK2 assembly by a biased intracellular agonist. Nature, 620:676-681, 2023 Cited by PubMed Abstract: Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands. The molecular assembly of GRKs on GPCRs and the basis of GRK-mediated biased signalling remain largely unknown owing to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gα and the arrestin-biased ligand SBI-553. The density map reveals the arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor transmembrane helix 6, analogous to the binding of the G protein to the receptor. SBI-553 binds at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of SBI-553 is compatible with arrestin binding but clashes with the binding of Gα protein, thus providing a mechanism for its arrestin-biased signalling capability. In sum, our structure provides a rational model for understanding the details of GPCR-GRK interactions and GRK2-mediated biased signalling. PubMed: 37532940DOI: 10.1038/s41586-023-06395-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.91 Å) |
Structure validation
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