Structural biology of G protein‐coupled receptor signaling complexes

A direct and functional interaction between the trimeric G protein Go and Rab5 in G proteincoupled receptor signaling

G protein coupled receptor signaling complexes in live cells

Classical models of receptor (GPCR) and G protein (Gαβγ) signaling based on biochemical studies have proposed that receptor stimulation results in G protein activation (Gα-GTP) and dissociation of the heterotrimer (Gα-GTP + Gβγ) to regulate downstream signaling events. Unclear is whether or not there exists freely diffusible, activated Gα-GTP on cellular membranes capable of catalytic signal am...

Structural biology of G protein-coupled receptors.

More than 60% of the current drugs are based on G protein-coupled receptors. Paradoxically, high-resolution structures are not available to facilitate rational drug design. Difficulties in expression, purification, and crystallization of these transmembrane receptors are the reasons for the low success rate. Recent individual and network-based technology development has significantly improved o...

Hybrid Molecular Mechanics/Coarse-Grained Simulations for Structural Prediction of G-Protein Coupled Receptor/Ligand Complexes

Understanding how ligands bind to G-protein coupled receptors (GPCRs) provides insights into a myriad of cell processes and is crucial for drug development. Here we extend a hybrid molecular mechanics/coarse-grained (MM/CG) approach applied previously to enzymes to GPCR/ligand complexes. The accuracy of this method for structural predictions is established by comparison with recent atomistic mo...

Activation of a G proteincoupled receptor by its endogenous ligand triggers the innate immune response of Caenorhabditis elegans

The innate defenses of the nematode Caenorhabditis elegans have diverged considerably from those of other animals. Perhaps most strikingly, C. elegans has lost the transcription factor NF-κB, key for defense in most animal species, and lacks functional orthologs of many known innate defense receptors1. On the other hand, core signaling pathways involved in innate immunity across a broad range o...