Stepwise activation of a metabotropic glutamate receptor

Kaavya Krishna Kumar (), Haoqing Wang, Chris Habrian, Naomi R. Latorraca, Jun Xu, Evan S. O’Brien, Chensong Zhang, Elizabeth Montabana, Antoine Koehl, Susan Marqusee, Ehud Y. Isacoff and Brian K. Kobilka ()
Additional contact information
Kaavya Krishna Kumar: Stanford University School of Medicine
Haoqing Wang: Stanford University School of Medicine
Chris Habrian: Stanford University School of Medicine
Naomi R. Latorraca: University of California, Berkeley
Jun Xu: Stanford University School of Medicine
Evan S. O’Brien: Stanford University School of Medicine
Chensong Zhang: SLAC National Accelerator Laboratory
Elizabeth Montabana: Stanford University School of Medicine
Antoine Koehl: Stanford University School of Medicine
Susan Marqusee: University of California, Berkeley
Ehud Y. Isacoff: University of California, Berkeley
Brian K. Kobilka: Stanford University School of Medicine

Nature, 2024, vol. 629, issue 8013, 951-956

Abstract: Abstract Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain1. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain2. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging, we reveal distinct receptor conformations upon allosteric modulator and G protein binding.

Date: 2024
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07327-x 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:629:y:2024:i:8013:d:10.1038_s41586-024-07327-x

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

DOI: 10.1038/s41586-024-07327-x

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 ().