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Selectivity determinants of GPCR-G-protein binding

Publication: Research - peer-reviewJournal article

Tilman Flock, Alexander S Hauser, Nadia Lund, David E Gloriam, Santhanam Balaji, M Madan Babu

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.

Original languageEnglish
JournalNature
Volume545
Issue number7654
Pages (from-to)317-322
Number of pages6
ISSN0028-0836
DOIs
StatePublished - 18 May 2017

    Research areas

  • Amino Acid Sequence, GPCR, Evolution, Molecular, G-protein-coupled receptor, G proteins, Structural Homology, Protein

ID: 183123626