Back to Search
Start Over
SIGNAL TRANSDUCTION. Structural basis for nucleotide exchange in heterotrimeric G proteins
- Source :
- Science (New York, N.Y.), vol 348, iss 6241
- Publication Year :
- 2015
- Publisher :
- eScholarship, University of California, 2015.
-
Abstract
- G protein-coupled receptors (GPCRs) relay diverse extracellular signals into cells by catalyzing nucleotide release from heterotrimeric G proteins, but the mechanism underlying this quintessential molecular signaling event has remained unclear. Here we use atomic-level simulations to elucidate the nucleotide-release mechanism. We find that the G protein α subunit Ras and helical domains-previously observed to separate widely upon receptor binding to expose the nucleotide-binding site-separate spontaneously and frequently even in the absence of a receptor. Domain separation is necessary but not sufficient for rapid nucleotide release. Rather, receptors catalyze nucleotide release by favoring an internal structural rearrangement of the Ras domain that weakens its nucleotide affinity. We use double electron-electron resonance spectroscopy and protein engineering to confirm predictions of our computationally determined mechanism.
- Subjects :
- Protein Structure
Secondary
General Science & Technology
1.1 Normal biological development and functioning
Chemical
Molecular Dynamics Simulation
Gi-Go
GTP-Binding Protein alpha Subunits
Gs
G-Protein-Coupled
Models
Underpinning research
Receptors
Humans
Guanine Nucleotide Exchange Factors
Generic health relevance
Tertiary
Signal Transduction
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Science (New York, N.Y.), vol 348, iss 6241
- Accession number :
- edsair.od.......325..ef086f3589d3d6bd38132055ad93bf63