Multiple 14-3-3 isoforms exist, and a GPCR can differentially interact with different 14-3-3 isoforms We found that some agonist-induced GPCR/14-3-3 signal intensities can rapidly decrease. Furthermore, we found that certain GPCR ligands can regulate GPCR/14-3-3 signals temporally, suggesting

,  Yongfeng Liu ,  Marion Lanier ,   Brian K Shoichet ,  Esther Martinborough ,  Jonathan F Fay ,  Can Cao ,   Bryan L Roth , et al. GPCR Events You can begin organizing and marking a few dates in 2025 .

their investigation on Molecular insights into G protein coupling specificity at a class A GPCR Jianjun Cao If you have any research you would like to showcase to our community, you can submit a poster presentation

DMS can be used to comprehensively assess the functional impact of mutations in a candidate protein, helping to validate whether drugs can effectively target it. This high-resolution mapping can confirm the protein’s role in disease pathology and highlight allosteric By examining how mutations in the target protein affect its interaction with the drug, researchers can Mutations in target proteins can lead to decreased drug affinity and/or potency, rendering treatments

These sites act as molecular switches that can modulate receptor activity, providing an untapped opportunity Allosteric ligands can be classified as positive allosteric modulators (PAMs), which increase the receptor Alternatively, they can function as neutral allosteric ligands (NALs), binding to a receptor's allosteric Moreover, they have the potential to enhance target selectivity, which can arise from greater sequence Allosteric agonists binding to intracellular sites can also promote G-protein signaling.

conformations, and the binding of a ligand, as well as interactions with signaling molecules like G proteins, can Natural and synthetic ligands can be categorized into four distinct efficacy classes: 1) full agonists produce the maximal response and can differ in intrinsic efficacy; 2) partial agonists are incapable neutral antagonists have null intrinsic efficacy, thus not affecting receptor signaling activity, and can Moreover, they have the potential to enhance target selectivity, which can arise from greater sequence

assays, signaling assays, cell imaging, protein structure determination, and omics applications, which can Classification: AI models can be used to distinguish GPCRs from non-GPCRs, and to classify GPCRs into Mutations: ML methods can determine stabilising mutations that enable structure determination and can Virtual screening: molecular docking and virtual screening can efficiently analyze large databases of Predicting GPCR properties: AI models can predict various properties of GPCRs, such as ligand binding

achieve this, the work of Heydenreich et al. (2023) will be analysed to demonstrate how mutagenesis can By identifying key β2AR residues that influence efficacy and potency, pharmaceutical researchers can For example, orthosteric drug design —in which drugs bind to the receptor’s primary active site—can now Alternatively, allosteric modulators , which bind to sites outside the traditional ligand-binding pocket, can Understanding the evolutionary conservation of these residues can lead to the development of drugs that

Redundancy can be exemplified by the tumor infiltration of Treg cells which can be driven directly by This redundancy can be seen as problematic in drug discovery as blocking a single receptor might not the chemokine-receptor system, different chemokines are able to activate different pathways, which can Signaling bias can be seen as complex as advantageous since selectively inhibiting certain signaling pathways while sparing others, can prevent some of the negative off-target effects.

“ A substitution of one amino acid by another in a protein can have effects ranging from negligible to While these structural techniques offer significant advantages in drug discovery, no single method can Furthermore, data on the role of specific residues within receptors can provide valuable insights for Through either random or targeted (site-directed) approaches, mutagenesis can provide a comprehensive In summary, mutagenesis can be a critical tool in drug discovery, particularly for studying GPCRs.

While these signaling pathways are highly interconnected, they can also be regulated independently (Kenakin In various pathological conditions, including cancer, aberrant ERK activity can lead to uncontrolled ERK activation pathways can be categorised into two main sub-pathways based on their subcellular localisation The choice of pathway can result in different cellular responses, underscoring the criticality of precise understanding the intricacies of GPCR signaling and utilising advanced assay technologies, researchers can

They can recognize cryptic epitopes often composed of discontinuous amino acid segments and occur only Nbs can stabilize specific conformations of proteins, including unstable structural intermediates and Generation, selection and functional expression: Nanobodies can be obtained by immunizing a camelid and Combinatorial biology methods such as phage display, yeast display, and ribosome display can be used Most Nbs can be functionally expressed as genetically encoded intrabodies within a eukaryotic cell.

While GPCRs can exist as monomers, some types, like class C GPCRs, are obligate dimers, either as homodimers class B GPCRs, however, has been more controversial, despite increasing evidence that these receptors can These dimeric forms, which can either be transient or stable, are believed to influence the function Recent studies suggest that class B1 GPCRs can form both homodimers and heterodimers, which may play

simultaneously interact with both Ser2777.42 and His2787.43, 2 only transiently contacts His2787.43, which can This approach can expand the repertoire of adenosine receptor antagonists that can be designed based

two reasons why researchers typically require years to uncover the mechanisms of disease before they can potential toxicities and side effects, and these key factors must be deemed tolerable before investigators can cells, has the drawback of causing damage to healthy cells in the process, leading to side effects that can

However, GLP-1R can also engage other G proteins, such as Gi/o and Gq/11, leading to different downstream Biased agonism at the GLP-1R has been extensively studied, revealing that different ligands can stabilize These differences in signaling profiles can have significant physiological implications. observed to reduce adipose tissue size more effectively than exendin, suggesting that biased agonism can

By using machine learning, AF2 can accurately predict the 3D structures of GPCRs with atomic-level accuracy concern is the reliance on data quality and quantity, where inaccuracies or biases in training data can Moreover, advanced AI models like AlphaFold3, which can predict complex protein-molecule interactions

In addition, VAMP2 can interact with other GPCRs, such as the beta-2 adrenergic receptor and the mu-opioid in the case of MOR, which is a receptor with several splicing variants, its traffic to the membrane can the integrity of its bi-leucine sequence (which is considered a key element in its recycling), which can receptor regulates pain perception and reward, the dysfunction in the MOR-SNARE complex interaction can You can consult the article at the following link: https://www.ecosystem.drgpcr.com/structural-and-molecular-insights-into-gpcr-function

During this process, APEX2 can label proteins in the vicinity, allowing the capture of a snapshot of When AUR is oxidized by APEX2 in the presence of H 2 O 2 , it produces a fluorescent product that can

Chemerin can signal via two G protein-coupled receptors, chem1 and chem2, as well as be bound to a third and secreted into the circulation as a precursor, but it is also expressed in some tissues where it can

Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors (GPCRs) and can Further, we show that 14 can be used as a tool for fragment-based screening approaches.

Mapping of Alphafold2 generated models of these proteins confirms that the same sites can be identified These sites cluster at nine distinct locations, and each can be found in many different proteins.

In the meantime, you can always check the  Classified GPCR News from the last weeks.

imparts many unresolved questions, such as the functional relevance of this localization, and whether H2R can contribute directly to transcriptional regulation and can affect lymphatic specific gene expression.

Keep in mind that you can always change your email preferences in your account settings. There is no limit to the number of posters we can accommodate, so hurry and submit your poster so that we can add it to the list of posters and increase the number of people who can ''stop by'' it on March

and SSAs regulating SST2 and SST5 homo- and hetero-dimer formation "The process of GPCR dimerization can SST2 and SST5 can also form endogenous hetero-dimers in these cells. In conclusion, we demonstrated that in GH3 cells SST2 and SST5 can form both homo- and hetero-dimers

excitatory neurotransmitter of the nervous central system, L-glutamate, and mGlu5 receptor activity can illustrate how access to high-resolution structures of GPCRs in complex with allosteric modulators can

Remember, you can always adjust your email preferences in your account settings. For Dr. There is no limit to the number of posters we can accommodate, so hurry and submit your poster so that we can add it to the list of posters and increase the number of people who can ''stop by'' it tomorrow