6D9H
Cryo-EM structure of the human adenosine A1 receptor-Gi2-protein complex bound to its endogenous agonist
Summary for 6D9H
| Entry DOI | 10.2210/pdb6d9h/pdb |
| EMDB information | 7835 |
| Descriptor | Guanine nucleotide-binding protein G(i) subunit alpha-2, 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, ... (5 entities in total) |
| Functional Keywords | signaling protein, membrane protein, active-state g protein-coupled receptor, adenosine a1 receptor |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 130702.62 |
| Authors | Draper-Joyce, C.J.,Khoshouei, M.,Thal, D.M.,Liang, Y.-L.,Nguyen, A.T.N.,Furness, S.G.B.,Venugopal, H.,Baltos, J.,Plitzko, J.M.,Danev, R.,Baumeister, W.,May, L.T.,Wootten, D.,Sexton, P.,Glukhova, A.,Christopoulos, A. (deposition date: 2018-04-29, release date: 2018-06-20, Last modification date: 2024-10-30) |
| Primary citation | Draper-Joyce, C.J.,Khoshouei, M.,Thal, D.M.,Liang, Y.L.,Nguyen, A.T.N.,Furness, S.G.B.,Venugopal, H.,Baltos, J.A.,Plitzko, J.M.,Danev, R.,Baumeister, W.,May, L.T.,Wootten, D.,Sexton, P.M.,Glukhova, A.,Christopoulos, A. Structure of the adenosine-bound human adenosine A1receptor-Gicomplex. Nature, 558:559-563, 2018 Cited by PubMed Abstract: The class A adenosine A receptor (AR) is a G-protein-coupled receptor that preferentially couples to inhibitory G heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 Å structure of the human AR in complex with adenosine and heterotrimeric G protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive AR, there is contraction at the extracellular surface in the orthosteric binding site mediated via movement of transmembrane domains 1 and 2. At the intracellular surface, the G protein engages the AR primarily via amino acids in the C terminus of the Gα α5-helix, concomitant with a 10.5 Å outward movement of the AR transmembrane domain 6. Comparison with the agonist-bound β adrenergic receptor-G-protein complex reveals distinct orientations for each G-protein subtype upon engagement with its receptor. This active AR structure provides molecular insights into receptor and G-protein selectivity. PubMed: 29925945DOI: 10.1038/s41586-018-0236-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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