7EQ1
GPR114-Gs-scFv16 complex
Summary for 7EQ1
| Entry DOI | 10.2210/pdb7eq1/pdb |
| EMDB information | 31254 |
| Descriptor | Gs protein alpha subunit, Adhesion G-protein coupled receptor G5, scFv16, ... (5 entities in total) |
| Functional Keywords | agpcr-g protein complex, structural protein |
| Biological source | Bos taurus (Bovine) More |
| Total number of polymer chains | 5 |
| Total formula weight | 147305.71 |
| Authors | |
| Primary citation | Ping, Y.Q.,Xiao, P.,Yang, F.,Zhao, R.J.,Guo, S.C.,Yan, X.,Wu, X.,Zhang, C.,Lu, Y.,Zhao, F.,Zhou, F.,Xi, Y.T.,Yin, W.,Liu, F.Z.,He, D.F.,Zhang, D.L.,Zhu, Z.L.,Jiang, Y.,Du, L.,Feng, S.Q.,Schoneberg, T.,Liebscher, I.,Xu, H.E.,Sun, J.P. Structural basis for the tethered peptide activation of adhesion GPCRs. Nature, 604:763-770, 2022 Cited by PubMed Abstract: Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes. Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence. Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with G: GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-β-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W and the constitution of a hydrogen-bond network formed by Q/Y and the P/VφφG motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and G coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common G-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with G. Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their G coupling. PubMed: 35418678DOI: 10.1038/s41586-022-04619-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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