The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region
Open accessAbstract
Class A G-protein-coupled receptors (GPCRs) are a large family of membrane proteins that mediate a wide variety of physiological functions, including vision, neurotransmission and immune responses. They are the targets of nearly one-third of all prescribed medicinal drugs such as beta blockers and antipsychotics. GPCR activation is facilitated by extracellular ligands and leads to the recruitment of intracellular G proteins. Structural rearrangements of residue contacts in the transmembrane domain serve as ‘activation pathways’ that connect the ligand-binding pocket to the G-protein-coupling region within the receptor. In order to investigate the similarities in activation pathways across class A GPCRs, we analysed 27 GPCRs from diverse subgroups for which structures of active, inactive or both states were available. Here we show that, despite the diversity in activation pathways between receptors, the pathways converge near the G-protein-coupling region. This convergence is mediated by a highly conserved structural rearrangement of residue contacts between transmembrane helices 3, 6 and 7 that releases G-protein-contacting residues. The convergence of activation pathways may explain how the activation steps initiated by diverse ligands enable GPCRs to bind a common repertoire of G proteins.
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Cites
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Self-citationJones, E. M., Lubock, N. B., Venkatakrishnan, A., Wang, J., Tseng, A. M., Paggi, J. M., Latorraca, N. R., Cancilla, D., Satyadi, M., Davis, J. E., et al. (2020) · eLife · doi:10.7554/elife.54895 · Cited by 168
Self-citationStructural determinants of co-translational protein complex assembly
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Liu, T., Ji, R.-L., & Tao, Y.-X. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108044 · Cited by 34
Leemann, S., & Kleinlogel, S. (2023) · doi:10.1101/2023.01.27.525823 · Cited by 2
Metadata
- Authors
- Venkatakrishnan, A. J., Deupi, X., Lebon, G., Heydenreich, F. M., Flock, T., Miljus, T., Balaji, S., Bouvier, M., Veprintsev, D. B., Tate, C. G., Schertler, G. F. X., & Babu, M. M.
- Venue
- Nature
- Published
- 2016-08
- Volume
- 536
- Issue
- 7617
- Pages
- 484-487
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2509928882
- Cited by
- 308
- References
- 4
- FWCI
- 18.66
- Type
- journal article
- Language
- en
- Open access
- green
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