Structural mechanism of ligand activation in human GABAB receptor

Yong Geng, Martin Bush, Lidia Mosyak, Feng Wang and Qing R. Fan ()
Additional contact information
Yong Geng: Columbia University
Martin Bush: Columbia University
Lidia Mosyak: Columbia University
Feng Wang: Columbia University
Qing R. Fan: Columbia University

Nature, 2013, vol. 504, issue 7479, 254-259

Abstract: Abstract Human GABAB (γ-aminobutyric acid class B) receptor is a G-protein-coupled receptor central to inhibitory neurotransmission in the brain. It functions as an obligatory heterodimer of the subunits GBR1 and GBR2. Here we present the crystal structures of a heterodimeric complex between the extracellular domains of GBR1 and GBR2 in the apo, agonist-bound and antagonist-bound forms. The apo and antagonist-bound structures represent the resting state of the receptor; the agonist-bound complex corresponds to the active state. Both subunits adopt an open conformation at rest, and only GBR1 closes on agonist-induced receptor activation. The agonists and antagonists are anchored in the interdomain crevice of GBR1 by an overlapping set of residues. An antagonist confines GBR1 to the open conformation of the inactive state, whereas an agonist induces its domain closure for activation. Our data reveal a unique activation mechanism for GABAB receptor that involves the formation of a novel heterodimer interface between subunits.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature12725 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:504:y:2013:i:7479:d:10.1038_nature12725

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

DOI: 10.1038/nature12725

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 ().