September 2022 Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca 2+ Sensing CaSR-GABAB1 and CaSR-GABAB2 chimeras subject to GABAB -dependent endoplasmic reticulum sorting to traffic mutant Transfected HEK-293 cells were assessed for Ca2+o -stimulated Ca2+i mobilization using mutations in either When the same mutation was present in both VFT domains of receptor dimers, analogous to homozygous neonatal Mutant heterodimers containing one wild-type (WT) and one mutant VFT domain, however, corresponding to

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine and compare the properties of S339fs5 with wild type CXCR4 and a previously identified WHIM syndrome mutant The S339fs5 and R334X mutants exhibited significantly increased signaling compared to wild type CXCR4 effectively inhibited by the CXCR4 antagonist TE-14016, this had no effect on the degradation of the WHIM mutants Taken together, these studies identify a new WHIM syndrome mutant, CXCR4-S339fs5, that promotes enhanced

Mutations in G protein-coupled receptors (GPCRs) underlie numerous diseases. Pharmacological chaperones are cell-permeant small molecules that engage nascent mutant GPCRs in the We previously demonstrated rescue of cell surface expression of luteinizing hormone receptor mutants Here we demonstrate that a similar approach can be employed to rescue mutant follicle-stimulating hormone acts as a pharmacological chaperone and can rescue cell surface expression and function of certain mutant

August 2022 Gαs and Gαq/11 protein coupling bias of two AVPR2 mutants (R68W and V162A) that cause nephrogenic diabetes insipidus "Loss-of-function mutations of the arginine vasopressin receptor 2 gene (AVPR2) cause Recent studies showed that some AVPR2 mutations could cause biased Gαq/11 protein coupling rather than In this study, R68W and V162A were analyzed to whether they show a bias to Gαs or Gαq/11 proteins. Studies about the Gα protein coupling bias of mutant AVPR2s may broaden our understanding of the relationship

Inhibition of autophagy by 3-methyladenine or interference of ATG5 or ATG7 attenuated HBx-induced cell cycle

October 2022 Mechanism of enhanced sensitivity of mutated β-adrenergic-like octopamine receptor to amitraz However, the underlying molecular mechanism of the enhanced sensitivity or toxicity of amitraz to mutated simulations are employed to explore the implied mechanism of the enhanced sensitivity to amitraz in mutant

October 2022 Design and validation of recombinant protein standards for quantitative Western blot analysis Replacement of radioligand binding assays with antibody-antigen interaction-based approaches for quantitative analysis This renders full-length recombinant GPCRs useless for analytical purposes, a problem that can be overcome C-terminal tail for use as standard and negative control, respectively, in quantitative Western blot analysis

2022 Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer cell cycle

September 2022 "Background Cancer driver genes are usually ranked by mutation frequency, which does We hypothesize that driver strength is higher for genes preferentially mutated in patients with few driver mutations overall, because these few mutations should be strong enough to initiate cancer. Strength Index (DSI) and the Normalized Driver Strength Index (NDSI), the latter independent of gene mutation

Recurrent high-impact mutations at cognate structural positions in class A G protein-coupled receptors Because there are many more GPCRs than effectors, mutations in different receptors could perturb signaling We hypothesized that somatic mutations in tumor samples may not be enriched within a single gene but To test this possibility, we systematically aggregated somatic cancer mutations across class A GPCRs Phenotypic characterization suggests these mutations induce perturbation of G protein activation and/

The differentially expressed genes (DEGs) and weighted correlation network analysis (WGCNA) were performed using R software, and functional enrichment analysis and protein–protein interaction (PPI) network were Module analysis was performed using Cytoscape.

September 2022 "MRAP2 is a small simple transmembrane protein arranged in a double antiparallel topology The aim of this work was to analyze the functional role of the specific arginine residue at position Results obtained with the MRAP2 mutants R125H and R125C, which are found in human patients with extreme

They can also function independently of GPCR activation upon acquiring mutations that prevent GTPase activity and result in constitutive signaling, as occurs with the αqQ209L mutation in uveal melanoma. could contribute to the mechanism of inhibition of αqQ209L by YM, we developed and examined N-terminal mutants αq is strongly inhibited by YM, demonstrating that resistance to YM inhibition by membrane-binding mutants

We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion

They employed a series of phospho-mimicking mutants and assays such as linear ion trap mass spectrometry Computational analyses indicated that these modifications favor the nucleotide-free state of Gαi. Notably, the Y320F mutation restored some signaling capabilities, emphasizing Tyr320's role in membrane

Through gene expression analysis in immune and gastrointestinal cells, we show that these isoforms emerge structural basis for this bias, we examined structural models of GPR35 and conducted experiments with mutants

April is the month of DNA Day, a special day commemorating the discovery of the DNA double helix structure The discovery of DNA's double helical structure was a scientific milestone that revolutionized molecular Furthermore, computational genomics approaches, such as structural bioinformatics analysis, have facilitated Phylogenetic analysis, paralogon groups, and fingerprints. Structural bioinformatics analysis of variants on GPCR function.

Cannabinoid Tolerance in S426A/S430A x β-Arrestin 2 Knockout Double-Mutant Mice. hypomineralization in mice by alteration of the expression of kallikrein-related peptidase 4 (Klk4) during pH cycling

Furthermore, the activating mutation in egl-30 encoding Gqα suppresses axon regeneration defective phenotype in acox-1.1 and srg-36 srg-37 mutants.

Cannabinoid tolerance in S426A/S430A x beta-arrestin 2 knock-out double mutant mice.

Mutant proteins were assayed to help reveal the basis of ligand specificity, and structural comparison

A knock-in mouse expressing a non-cleavable GPR116 mutant phenocopies the pulmonary phenotype of GPR116

Using several bioinformatics tools to evaluate the impact of mutations, we found that nsSNPs rs35106420 Docking analysis of rs35106420, harbored in the ADGLR3-hormone receptor domain (HRM, a common extracellular GIP has been linked to the pathogenesis of diabetes mellitus, and our analyses suggest a potential link Overall, the comprehensive application of bioinformatics tools showed that functional mutations in the

We found that RGS complexes with Kel1 and prefers the unphosphorylatable RGS mutant.

A case for (mutant) G protein-coupled receptors Reviews, GPCRs, and more RGS2 and female common diseases G protein-coupled receptor, and renin-angiotensin system autoantibodies: Systematic review and meta-analysis Structural and Molecular Insights into GPCR Function Analysis of the Dynamics of the Human Growth Hormone of the Molecule Focused classifications and refinements in high-resolution single particle cryo-EM analysis

Targeting rhodopsin with small molecule chaperones to improve the folding and stability of the mutant

This voltage dependent potentiation is abolished in mutant animals expressing a voltage independent receptor

via distinct components of its signalling repertoire Common to all cytomegalovirus (CMV) genomes analysed Identification of a MCMV M33 mutant (M33ΔC38) for which CREB signalling was disabled, but PLCβ activation All cytomegalovirus (CMV) genomes analysed to date possess GPCR homologs with phylogenetic evidence for