ligand activity
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Author(s):  
Michael C. Robitaille ◽  
Joseph A. Christodoulides ◽  
Patrick J. Calhoun ◽  
Jeff M. Byers ◽  
Marc P. Raphael

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Berenice Ziegler ◽  
Irene Yiallouros ◽  
Benjamin Trageser ◽  
Sumit Kumar ◽  
Moritz Mercker ◽  
...  

Abstract Background The Hydra head organizer acts as a signaling center that initiates and maintains the primary body axis in steady state polyps and during budding or regeneration. Wnt/beta-Catenin signaling functions as a primary cue controlling this process, but how Wnt ligand activity is locally restricted at the protein level is poorly understood. Here we report a proteomic analysis of Hydra head tissue leading to the identification of an astacin family proteinase as a Wnt processing factor. Results Hydra astacin-7 (HAS-7) is expressed from gland cells as an apical-distal gradient in the body column, peaking close beneath the tentacle zone. HAS-7 siRNA knockdown abrogates HyWnt3 proteolysis in the head tissue and induces a robust double axis phenotype, which is rescued by simultaneous HyWnt3 knockdown. Accordingly, double axes are also observed in conditions of increased Wnt activity as in transgenic actin::HyWnt3 and HyDkk1/2/4 siRNA treated animals. HyWnt3-induced double axes in Xenopus embryos could be rescued by coinjection of HAS-7 mRNA. Mathematical modelling combined with experimental promotor analysis indicate an indirect regulation of HAS-7 by beta-Catenin, expanding the classical Turing-type activator-inhibitor model. Conclusions We show the astacin family protease HAS-7 maintains a single head organizer through proteolysis of HyWnt3. Our data suggest a negative regulatory function of Wnt processing astacin proteinases in the global patterning of the oral-aboral axis in Hydra.


2021 ◽  
Author(s):  
Michael C. Robitaille ◽  
Joseph A. Christodoulides ◽  
Patrick Calhoun ◽  
Jeff M. Byers ◽  
Marc P. Raphael

AbstractSurface ligand activity is a key design parameter for successfully interfacing surfaces with cells - whether in the context of in vitro investigations for understanding cellular signaling pathways or more applied applications in drug delivery and medical implants. Unlike other crucial surface parameters, such as stiffness and roughness, surface ligand activity currently lacks a standardized measurement approach that can be readily paired with live cell investigations. To fill this void, we have developed a concurrent control technique for characterizing in vitro ligand surface activity. Pairs of gold-coated glass chips were biofunctionalized with RGD ligand in a parallel workflow: one chip for in vitro applications and the other for surface plasmon resonance (SPR) based RGD activity characterization. Recombinant αVβ3 integrins were injected over the SPR chip surface as mimics of the cellular membrane bound receptors and the resulting binding kinetics parameterized to quantify ligand activity. These activity measurements were correlated with cell morphological features, measured by interfacing MDA-MB-231 cells with the in vitro chip surfaces on the live cell microscope. We show that the SPR concurrent control approach has multiple advantages based on the facts that SPR is a standardized technique and has the sensitivity to measure ligand activity across the most relevant range of extracellular surface densities. Furthermore, by pairing both SPR and in vitro approaches, a comparison of the results can provide biological insights into the nature of cellular adhesion and dynamics.


Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 38
Author(s):  
Evangelia Sereti ◽  
Chrisiida Tsimplouli ◽  
Elisavet Kalaitsidou ◽  
Nikos Sakellaridis ◽  
Konstantinos Dimas

Sigma (σ) receptors have attracted great interest since they are implicated in various cellular functions and biological processes and diseases, including various types of cancer. The receptor family consists of two subtypes: sigma-1 (σ1) and sigma-2 (σ2). Both σ receptor subtypes have been proposed as therapeutic targets for various types of cancers, and many studies have provided evidence that their selective ligands (agonists and antagonists) exhibit antiproliferative and cytotoxic activity. Still, the precise mechanism of action of both σ receptors and their ligands remains unclear and needs to be elucidated. In this study, we aimed to simultaneously determine the expression levels of both σ receptor subtypes in several human cancer cell lines. Additionally, we investigated the in vitro antiproliferative activity of some widely used σ1 and σ2 ligands against those cell lines to study the relationship between σ receptor expression levels and σ ligand activity. Finally, we ran the NCI60 COMPARE algorithm to further elucidate the cytotoxic mechanism of action of the selected σ ligands studied herein.


2020 ◽  
Author(s):  
Jing-Fang Yang ◽  
Meng-Yao Wang ◽  
Di Wang ◽  
Jing-Yi Li ◽  
Ge-Fei Hao ◽  
...  

Abstract Cation-π interactions widely exist between ligand-protein interfaces, attracting much attention in molecular recognition in recent years. Interactions named cation-π and π-cation (cationic vs arene small molecular ligands) shall be separately considered in drug and pesticide design process. The two interactions involved in ligands and protein pockets may differ in energy features and therefore offers significant inspiration for drug and pesticide design. However, an in-depth study on differences between cation-π and π-cation systems from an energy perspective is still lacking. In this study, we calculated and compared cation-π and π-cation systems in terms of physicochemical properties of ligand/protein and solvation effect. It seems that the desolvation penalty of the cation-π systems was relatively higher than the π-cation pairs, even though these interactions both can improve the ligand activity. This is the reason for evolution converged on π-cation interactions in the cation-π-mediated proteins. The π-cation interaction facilitating the inhalation of ligand to the pocket may provide a new sight for the molecular design of pharmaceuticals and pesticides.


Foods ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 793 ◽  
Author(s):  
Raquel Ruiz ◽  
Raquel Olías ◽  
Alfonso Clemente ◽  
Luis A. Rubio

Legume consumption has been reported to induce beneficial effects on obesity-associated metabolic disorders, but the underlying mechanisms have not been fully clarified. In the current work, pea (Pisum sativum L.) seed meal proteins (albumins, legumins and vicilins) were isolated, submitted to a simulated gastrointestinal digestion, and the effects of their hydrolysates (pea albumins hydrolysates (PAH), pea legumins hydrolysates (PLH) and pea vicilin hydrolysates (PVH), respectively) on 3T3-L1 murine pre-adipocytes were investigated. The pea vicilin hydrolysate (PVH), but not native pea vicilins, increased lipid accumulation during adipocyte differentiation. PVH also increased the mRNA expression levels of the adipocyte fatty acid-binding protein (aP2) and decreased that of pre-adipocyte factor-1 (Pref-1) (a pre-adipocyte marker gene), suggesting that PVH promotes adipocyte differentiation. Moreover, PVH induced adiponectin and insulin-responsive glucose transporter 4 (GLUT4) and stimulated glucose uptake. The expression levels of peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of adipocyte differentiation, were up-regulated in 3T3-L1 cells treated with PVH during adipocyte differentiation. Finally, PVH exhibited PPARγ ligand activity. Lactalbumin or other pea hydrolysates (PAH, PLH) did not exhibit such effects. These findings show that PVH stimulates adipocyte differentiation via, at least in part, the up-regulation of PPARγ expression levels and ligand activity. These effects of PVH might be relevant in the context of the beneficial health effects of legume consumption in obesity-associated metabolic disorders.


2020 ◽  
Vol 19 (6) ◽  
pp. 854-857
Author(s):  
Cuncun Zhou ◽  
Yunfan Ji ◽  
Liping Ren ◽  
Xusheng Shao

In order to achieve light regulation of biological functions, a series of photoswitchable azobenzene-based meta-diamide analogues were synthesized. One of the ABMDAs can lead to activity changes towards Aedes albopictus larvae upon photoisomerization and enables optical modulation of membrane potential of DUM neurons.


2020 ◽  
Vol 89 (4) ◽  
pp. 384-393
Author(s):  
Fatema Tuz Zohra ◽  
Yuri Tominaga ◽  
Yomi Matsumoto ◽  
Naoko Taguchi ◽  
Ai Okubo ◽  
...  

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