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Department of Pharmacology

 

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Read more at: 5-oxoETE triggers nociception in constipation predominant irritable bowel syndrome through MAS-related G protein coupled receptor D

5-oxoETE triggers nociception in constipation predominant irritable bowel syndrome through MAS-related G protein coupled receptor D

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites such as prostaglandin E2 (PGE2) are elevated in IBS and implicated in visceral hypersensitivity. The aim of this study was to quantify PUFA metabolites in IBS patients and evaluate their role in pain.


Read more at: RAMP3 determines rapid recycling of atypical chemokine receptor-3 for guided angiogenesis.

RAMP3 determines rapid recycling of atypical chemokine receptor-3 for guided angiogenesis.

Receptor-activity-modifying proteins (RAMPs) are single transmembrane-spanning proteins which serve as molecular chaperones and allosteric modulators of G-protein-coupled receptors (GPCRs) and their signaling pathways. Although RAMPs have been previously studied in the context of their effects on Family B GPCRs, the coevolution of RAMPs with many GPCR families suggests an expanded repertoire of potential interactions.


Read more at: Unraveling the Mechanics of a Repeat-Protein Nanospring — From Folding of Individual Repeats to Fluctuations of the Superhelix

Unraveling the Mechanics of a Repeat-Protein Nanospring — From Folding of Individual Repeats to Fluctuations of the Superhelix

Tandem-repeat proteins comprise small secondary structure motifs that stack to form one- dimensional arrays with distinctive mechanical properties that are proposed to direct their cellular functions. Here, we use single-molecule optical tweezers to study the folding of consensus-designed tetratricopeptide repeats (CTPRs) — superhelical arrays of short helix-turn-helix motifs. We find that CTPRs display a spring-like mechanical response in which individual repeats undergo rapid equilibrium fluctuations between partially folded and unfolded conformations.


Read more at: Engineering mono- and multi-valent inhibitors on a modular scaffold

Engineering mono- and multi-valent inhibitors on a modular scaffold

Here we exploit the simple, ultra-stable, modular architecture of consensus-designed tetratricopeptide repeat proteins (CTPRs) to create a platform capable of displaying both single as well as multiple functions and with diverse programmable geometrical arrangements by grafting non-helical short linear binding motifs (SLiMs) onto the loops between adjacent repeats. As proof of concept, we built synthetic CTPRs to bind and inhibit the human tankyrase proteins (hTNKS), which play a key role in Wnt signaling and are upregulated in cancer.


Read more at: Probing the unfolded protein response in long-lived naked mole-rats

Probing the unfolded protein response in long-lived naked mole-rats

The long-living naked mole-rat (NMR) shows negligible senescence and resistance to age-associated diseases. Recent evidence, based on protein-level assays, suggests that enhanced protein homeostasis machinery contributes to NMR stress-resistance and longevity. Here, we develop NMR-specific, transcriptional assays for measuring the unfolded protein response (UPR), a component of ER proteostasis.