Structural basis for nucleotide exchange in heterotrimeric G proteins

Autor:	Daniel H. Arlow, Zhongyu Yang, Aashish Manglik, David W. Borhani, Ansgar Philippsen, Thomas J. Mildorf, Michael T. Lerch, Brian K. Kobilka, Daniel Hilger, Wayne L. Hubbell, Roger K. Sunahara, Ron O. Dror, David E. Shaw, Nicolas Villanueva
Rok vydání:	2015
Předmět:	Multidisciplinary Protein structure Biochemistry G protein GTP-Binding Protein alpha Subunits Heterotrimeric G protein Biophysics Guanine nucleotide exchange factor Protein engineering Biology Signal transduction G protein-coupled receptor
Zdroj:	Science. 348:1361-1365
ISSN:	1095-9203 0036-8075
Popis:	How a receptor transmits a signal G protein–coupled receptors (GPCRs) transmit diverse external signals into the cell. When activated by an outside stimulus, they bind to a G protein inside the cell and accelerate exchange of a bound guanosine diphosphate (GDP) nucleotide for guanosine triphosphate, which initiates intercellular signaling. Dror et al. used atomic-level molecular dynamics simulations to show how GPCRs enhance GDP release. The G protein is dynamic and frequently adopts a conformation that exposes GDP even without the receptor bound. GPCR binding to this conformation favors an additional structural rearrangement that favors GDP release. The authors confirmed these predictions experimentally using double electron-electron resonance spectroscopy. Science , this issue p. 1361
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::7852d194960b30cbaad9f4b830f27dbe https://doi.org/10.1126/science.aaa5264 Zobrazit plný text záznamu Plný text ve formátu PDF