Structure of the adenosine-bound human adenosine A1 receptor–Gi complex

Christopher J. Draper-Joyce, Maryam Khoshouei, David M. Thal, Yi-Lynn Liang, Anh T. N. Nguyen, Sebastian G. B. Furness, Hariprasad Venugopal, Jo-Anne Baltos, Jürgen M. Plitzko, Radostin Danev, Wolfgang Baumeister, Lauren T. May, Denise Wootten, Patrick M. Sexton (), Alisa Glukhova () and Arthur Christopoulos ()
Additional contact information
Christopher J. Draper-Joyce: Monash Institute of Pharmaceutical Sciences, Monash University
Maryam Khoshouei: Max Planck Institute of Biochemistry
David M. Thal: Monash Institute of Pharmaceutical Sciences, Monash University
Yi-Lynn Liang: Monash Institute of Pharmaceutical Sciences, Monash University
Anh T. N. Nguyen: Monash Institute of Pharmaceutical Sciences, Monash University
Sebastian G. B. Furness: Monash Institute of Pharmaceutical Sciences, Monash University
Hariprasad Venugopal: Monash University, Clayton
Jo-Anne Baltos: Monash Institute of Pharmaceutical Sciences, Monash University
Jürgen M. Plitzko: Max Planck Institute of Biochemistry
Radostin Danev: Max Planck Institute of Biochemistry
Wolfgang Baumeister: Max Planck Institute of Biochemistry
Lauren T. May: Monash Institute of Pharmaceutical Sciences, Monash University
Denise Wootten: Monash Institute of Pharmaceutical Sciences, Monash University
Patrick M. Sexton: Monash Institute of Pharmaceutical Sciences, Monash University
Alisa Glukhova: Monash Institute of Pharmaceutical Sciences, Monash University
Arthur Christopoulos: Monash Institute of Pharmaceutical Sciences, Monash University

Nature, 2018, vol. 558, issue 7711, 559-563

Abstract: Abstract The class A adenosine A1 receptor (A1R) is a G-protein-coupled receptor that preferentially couples to inhibitory Gi/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 Gi2 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 Gαi α5-helix, concomitant with a 10.5 Å outward movement of the A1R transmembrane domain 6. Comparison with the agonist-bound β2 adrenergic receptor–Gs-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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (10)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0236-6 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:558:y:2018:i:7711:d:10.1038_s41586-018-0236-6

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0236-6

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().