Comprehensive Analysis of Non-Synonymous Natural Variants of G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs. Despite the clinical importance of GPCRs, studies on the genotype-phenotype relationship of GPCR natural variants have been limited to a few GPCRs such as β-adrenergic receptors and opioid receptors. Comprehensive understanding of non-synonymous natural variations within GPCRs would help to predict the unknown genotype-phenotype relationship and yet-to-be-discovered natural variants. Here, we analyzed the non-synonymous natural variants of all non-olfactory GPCRs available from a public database, UniProt. The results suggest that non-synonymous natural variations occur extensively within the GPCR superfamily especially in the N-terminus and transmembrane domains. Within the transmembrane domains, natural variations observed more frequently in the conserved residues, which leads to disruption of the receptor function. Our analysis also suggests that only few non-synonymous natural variations have been studied in efforts to link the variations with functional consequences.

Recent Progress in Understanding the Conformational Mechanism of Heterotrimeric G Protein Activation

Heterotrimeric G proteins are key intracellular coordinators that receive signals from cells through activation of cognate G protein-coupled receptors (GPCRs). The details of their atomic interactions and structural mechanisms have been described by many biochemical and biophysical studies. Specifically, a framework for understanding conformational changes in the receptor upon ligand binding and associated G protein activation was provided by description of the crystal structure of the β2-adrenoceptor-Gs complex in 2011. This review focused on recent findings in the conformational dynamics of G proteins and GPCRs during activation processes.

Chemical study on Crateva advansonnii DC (Capparaceae)

Crateva advansonnii DC.-Capparaceae is a medicinal plant which has been used as an antidote for snakebite in Tay Ninh province and in Cambodia. The chemical study on the bark of this plant led to the isolation as a triperpen with structure was unambigously determined as epi-lupeol by UV, IR and NMR spectral data

Tetracyclic diterpene from Macaranga triloba (Blume) Muell-Arg

Grayanatoxin IV, a tetracyclic diterpenoid, was isolated from the leaves of Macaranga triloba for the first time. Its structure was elucidated on the basis of spectral analysis including1H-NMR,13CNMR and 2D-NMR techniques in comparison with 13CNMR data of the authentic compound

Determination of Major Saponins in panax notoginseng and Its Preparations by HPLC

Reverse phase high performance liquid chromatography method for separation and quantitative determination of major saponins in Panax notoginseng (Burk) F.H. Chen. and its pharmaceutical preparations was described. The quantitative results of saponins (gingsenosides Rg1, Re, Rd, Rb1 and notoginsenoside R1) were given