Summary for 9BUY
| Entry DOI | 10.2210/pdb9buy/pdb |
| EMDB information | 44925 |
| Descriptor | Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (8 entities in total) |
| Functional Keywords | gpcr, signaling protein-immune system complex, signaling protein/immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 167730.77 |
| Authors | |
| Primary citation | Casiraghi, M.,Wang, H.,Brennan, P.C.,Habrian, C.,Hubner, H.,Schmidt, M.F.,Maul, L.,Pani, B.,Bahriz, S.M.F.M.,Xu, B.,Staffen, N.,Assafa, T.E.,Chen, B.,White, E.,Sunahara, R.K.,Inoue, A.,Xiang, Y.K.,Lefkowitz, R.J.,Isacoff, E.Y.,Nucci, N.,Gmeiner, P.,Lerch, M.T.,Kobilka, B.K. Structure and dynamics determine G protein coupling specificity at a class A GPCR. Sci Adv, 11:eadq3971-eadq3971, 2025 Cited by PubMed Abstract: G protein-coupled receptors (GPCRs) exhibit varying degrees of selectivity for different G protein isoforms. Despite the abundant structures of GPCR-G protein complexes, little is known about the mechanism of G protein coupling specificity. The β-adrenergic receptor is an example of GPCR with high selectivity for Gαs, the stimulatory G protein for adenylyl cyclase, and much weaker for the Gαi family of G proteins inhibiting adenylyl cyclase. By developing a Gαi-biased agonist (LM189), we provide structural and biophysical evidence supporting that distinct conformations at ICL2 and TM6 are required for coupling of the different G protein subtypes Gαs and Gαi. These results deepen our understanding of G protein specificity and bias and can accelerate the design of ligands that select for preferred signaling pathways. PubMed: 40106559DOI: 10.1126/sciadv.adq3971 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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