PDBsum entry 6d9h

Signaling protein

PDB id: 6d9h

Contents

Protein chains

209 a.a.

338 a.a.

57 a.a.

288 a.a.

Ligands

ADN

References listed in PDB file

Key reference

• Title: Structure of the adenosine-Bound human adenosine a₁ receptor-G_i complex.
• Authors: C.J.Draper-Joyce, M.Khoshouei, D.M.Thal, Y.L.Liang, A.T.N.Nguyen, S.G.B.Furness, H.Venugopal, J.A.Baltos, J.M.Plitzko, R.Danev, W.Baumeister, L.T.May, D.Wootten, P.M.Sexton, A.Glukhova, A.Christopoulos.
• Ref.: Nature, 2018, 558, 559-563. [DOI no: 10.1038/s41586-018-0236-6]
• PubMed id: 29925945

Abstract

The class A adenosine A₁ receptor (A₁R) is a G-protein-coupled receptor that preferentially couples to inhibitory G_i/o heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 Å structure of the human A₁R in complex with adenosine and heterotrimeric G_i2 protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive A₁R, 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 A₁R primarily via amino acids in the C terminus of the Gα_i α5-helix, concomitant with a 10.5 Å outward movement of the A₁R transmembrane domain 6. Comparison with the agonist-bound β₂ adrenergic receptor-G_s-protein complex reveals distinct orientations for each G-protein subtype upon engagement with its receptor. This active A₁R structure provides molecular insights into receptor and G-protein selectivity.