Selectivity determinants of GPCR–G-protein binding

Tilman Flock (), Alexander S. Hauser, Nadia Lund, David E. Gloriam, Santhanam Balaji and M. Madan Babu ()
Additional contact information
Tilman Flock: MRC Laboratory of Molecular Biology
Alexander S. Hauser: University of Copenhagen
Nadia Lund: University of Copenhagen
David E. Gloriam: University of Copenhagen
Santhanam Balaji: MRC Laboratory of Molecular Biology
M. Madan Babu: MRC Laboratory of Molecular Biology

Nature, 2017, vol. 545, issue 7654, 317-322

Abstract: Abstract The selective coupling of G-protein-coupled receptors (GPCRs) to specific G proteins is critical to trigger the appropriate physiological response. However, the determinants of selective binding have remained elusive. Here we reveal the existence of a selectivity barcode (that is, patterns of amino acids) on each of the 16 human G proteins that is recognized by distinct regions on the approximately 800 human receptors. Although universally conserved positions in the barcode allow the receptors to bind and activate G proteins in a similar manner, different receptors recognize the unique positions of the G-protein barcode through distinct residues, like multiple keys (receptors) opening the same lock (G protein) using non-identical cuts. Considering the evolutionary history of GPCRs allows the identification of these selectivity-determining residues. These findings lay the foundation for understanding the molecular basis of coupling selectivity within individual receptors and G proteins.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (9)

Downloads: (external link)
https://www.nature.com/articles/nature22070 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:545:y:2017:i:7654:d:10.1038_nature22070

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

DOI: 10.1038/nature22070

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 ().