Active-State Models of Ternary GPCR Complexes: Determinants of Selective Receptor-G-Protein Coupling

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Kling R, Lanig H, Clark T, Gmeiner P
Zeitschrift: PLoS ONE
Verlag: Public Library of Science
Jahr der Veröffentlichung: 2013
Band: 8
Heftnummer: 6
ISSN: 1932-6203
Sprache: Englisch


Abstract


Based on the recently described crystal structure of the β adrenergic receptor - G-protein complex, we report the first molecular-dynamics simulations of ternary GPCR complexes designed to identify the selectivity determinants for receptor-G-protein binding. Long-term molecular dynamics simulations of agonist-bound β2AR-Gα and D2R-Gα complexes embedded in a hydrated bilayer environment and computational alanine-scanning mutagenesis identified distinct residues of the N-terminal region of intracellular loop 3 to be crucial for coupling selectivity. Within the G-protein, specific amino acids of the α5-helix, the C-terminus of the Gα-subunit and the regions around αN-β1 and α4-β6 were found to determine receptor recognition. Knowledge of these determinants of receptor-G-protein binding selectivity is essential for designing drugs that target specific receptor/G-protein combinations. © 2013 Kling et al.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Clark, Timothy apl. Prof. Dr.
Computer-Chemie-Centrum
Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Kling, Ralf
Lehrstuhl für Pharmazeutische Chemie
Lanig, Harald PD Dr.
Computer-Chemie-Centrum


Zusätzliche Organisationseinheit(en)
Emil-Fischer-Zentrum (Emil Fischer Center)


Zitierweisen

APA:
Kling, R., Lanig, H., Clark, T., & Gmeiner, P. (2013). Active-State Models of Ternary GPCR Complexes: Determinants of Selective Receptor-G-Protein Coupling. PLoS ONE, 8(6). https://dx.doi.org/10.1371/journal.pone.0067244

MLA:
Kling, Ralf, et al. "Active-State Models of Ternary GPCR Complexes: Determinants of Selective Receptor-G-Protein Coupling." PLoS ONE 8.6 (2013).

BibTeX: 

Zuletzt aktualisiert 2018-09-08 um 01:56