The dynamic basis of G-protein recognition and activation by a GPCR - PubMed
14 hours ago
- #cryo-electron microscopy
- #GPCR
- #G-protein
- Study presents cryo-electron microscopy structures of human neurotensin receptor type 1 (NTSR1) with Go and Gq, showing dynamic rearrangements for G-protein subtype accommodation.
- Time-resolved cryo-electron microscopy analyses of NTSR1-Gi visualize G-protein dissociation processes upon GDP/GTP binding, identifying over 20 intermediates.
- Four key mechanistic features identified: GDP/GTP-induced Gi release from canonical and non-canonical conformations, common intracellular rearrangements for G-protein recognition, stepwise Gβγ separation, and distinct dissociation pathways for Gi and Gs.
- Findings provide a framework for understanding GPCR signalling dynamics and aiding in therapeutic development.