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

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/

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 Seventeen FSHR mutations described in patients with reproductive dysfunction were expressed in HEK 293T These findings aid in advancing the understanding of the effects of genetic mutations on GPCR function

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine While several gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor CXCR4 have been identified in WHIM syndrome patients, the functional effect of these mutations are not fully understood. Here, we report on a new WHIM syndrome mutation that results in a frame shift within the codon for Ser339

interactions between VFT units and HH bundles, and the impacts of heterozygous or homozygous inactivating mutations 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 insufficient for maximal signaling and there was no functional difference between heterodimers in which the mutation

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 give insights into the relationship between the conformational change of the receptor because of the mutation Studies about the Gα protein coupling bias of mutant AVPR2s may broaden our understanding of the relationship

September 2022 "Over 100 mutations in the rhodopsin gene have been linked to a spectrum of retinopathies most of these variants exhibit a loss of function, the molecular defects caused by these underlying mutations In this work, we utilize deep mutational scanning to quantitatively compare the plasma membrane expression However, the magnitude of the response to this molecule varies considerably across this spectrum of mutations

form of Kallmann syndrome (KS), characterized by hypogonadotropic hypogonadism and anosmia, is due to mutations activation of the G protein-coupled receptors (GPCRs) prokineticin receptor 1 and 2 (PKR1, 2), and mutations modulatory activity, although data from GST pull-down (glutathione-S-transferase) and analysis of the N267K mutation

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

Through an in-depth mutational analysis of β2AR, the researchers identified specific residues that influence that residues critical for β2AR function are under intense selective pressure, while others are more mutation-tolerant Deep mutational scanning, for instance, is gaining popularity as a strategy due to its ability to comprehensively

In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation.

Using several bioinformatics tools to evaluate the impact of mutations, we found that nsSNPs rs35106420 Overall, the comprehensive application of bioinformatics tools showed that functional mutations in the

Direct activation of PKC and mutation of rat mGlu5a Ser901, a PKC-dependent phosphorylation site in the Gαq/11 inhibitor YM-254890, GPCR kinase 2 and 3 (GRK2 and GRK3) KO cells, and a receptor containing a mutated

Eliminating β2AR S-nitrosylation by mutation of C265 augments β2AR protein kinase A signaling, enables

Cholesterol bound to the amino-terminal permease-like region of LYCHOS, and mutating this site impaired

This single point mutation in extracellular loop 2 of the β 2AR is sufficient to intrinsically bias the We characterized the effects of extracellular loop mutations on agonist-promoted interactions of GPCRs

We also take into account the detrimental effect of mutations carried by distinct signalling proteins

Mutations within the oxysterol binding site and the Gαi interface attenuate G protein signaling and abolish

A detailed analysis of the engagements allows us to design mutations that specifically enhance one pathway

We combined in vitro and in situ chemical crosslinking, disulfide pattern analysis, and mutation data

In addition, hearing loss can be caused by mutations of certain GPCRs, such as Vlgr1, Gpr156, S1P2, and

Mutations in VLGR1 have been associated with the human Usher syndrome (USH), the most common form of

Mandibulofacial dysostosis with alopecia results from ETAR gain-of-function mutations via allosteric Reviews, GPCRs, and more Single nucleotide variations encoding missense mutations in G protein-coupled

Additionally, deep mutational scanning can generate large-scale datasets, allowing researchers to determine Deep mutational scanning: a new style of protein science. Nature Methods , 11 (8), 801-807.

Cellular functional studies with mutations of β1-AR residues show effects on the cellular signaling from

antibody showing preclinical efficacy against all COVID-19 variants, including the delta and omicron mutations

Mutations in the MC4R are the most frequent monogenic cause for obesity.