Selectivity determinants of GPCR-G-protein binding
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Selectivity determinants of GPCR-G-protein binding. / Flock, Tilman; Hauser, Alexander S; Lund, Nadia; Gloriam, David E; Balaji, Santhanam; Babu, M Madan.
I: Nature, Bind 545, Nr. 7654, 18.05.2017, s. 317-322.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Selectivity determinants of GPCR-G-protein binding
AU - Flock, Tilman
AU - Hauser, Alexander S
AU - Lund, Nadia
AU - Gloriam, David E
AU - Balaji, Santhanam
AU - Babu, M Madan
PY - 2017/5/18
Y1 - 2017/5/18
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - GPCR
KW - Evolution, Molecular
KW - G-protein-coupled receptor
KW - G proteins
KW - Structural Homology, Protein
U2 - 10.1038/nature22070
DO - 10.1038/nature22070
M3 - Journal article
C2 - 28489817
VL - 545
SP - 317
EP - 322
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7654
ER -
ID: 183123626