A5045852499- Receptor Mechanisms and Signaling
- Metabolism, Diabetes, and Cancer
- Advanced biosensing and bioanalysis techniques
- Pancreatic function and diabetes
- Protein Degradation and Inhibitors
- PI3K/AKT/mTOR signaling in cancer
- Advanced Biosensing Techniques and Applications
- Force Microscopy Techniques and Applications
- Diabetes and associated disorders
- Cellular transport and secretion
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Molecular Junctions and Nanostructures
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Cellular Mechanics and Interactions
- Advanced Fluorescence Microscopy Techniques
- Carbon Nanotubes in Composites
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
Pohang University of Science and Technology
2013-2023
Korea Post
2020
Metformin is the first-line therapy for type 2 diabetes, but there are large inter-individual variations in responses to this drug. Its mechanism of action not fully understood, activation AMP-activated protein kinase (AMPK) and changes gut microbiota appear be important. The inhibitory role microbial metabolites on metformin has previously been investigated. Here, we show that concentrations metabolite imidazole propionate higher subjects with diabetes taking who have high blood glucose. We...
Membrane nanotubes or tunneling (TNTs) that connect cells have been recognized as a previously unidentified pathway for intercellular transport between distant cells. However, it is unknown how this delicate structure, which extends over tens of micrometers and remains robust hours, formed. Here, we found TNT develops from double filopodial bridge (DFB) created by the physical contact two filopodia through helical deformation DFB. The transition DFB to close-ended most likely triggered...
Due to their high affinity and specificity, aptamers have been widely used as effective inhibitors in clinical applications. However, the ability activate protein function through aptamer-protein interaction has not well-elucidated. To investigate potential target-specific agonists, we SELEX generate insulin receptor (IR) identified an agonistic aptamer named IR-A48 that specifically binds IR, but IGF-1 receptor. Despite its capacity stimulate IR autophosphorylation, similar insulin, found...
Abstract Activation of insulin receptor (IR) initiates a cascade conformational changes and autophosphorylation events. Herein, we determined three structures IR trapped by aptamers using cryo-electron microscopy. The A62 agonist aptamer selectively activates metabolic signaling. In the absence insulin, two agonists adopt an insulin-accessible arrowhead conformation mimicking site-1/site-2’ coordination. Insulin binding at one site triggers in protomer, but this movement is blocked other...
Insulin resistance is a syndrome that affects multiple insulin target tissues, each having different biological functions regulated by insulin. A remaining question to mechanistically explain how an cell/tissue can be resistant in one function and sensitive another at the same time. Here, we provide evidence pancreatic β cells, knockdown of PI3K-C2α expression results rerouting signal from receptor (IR)-B/PI3K-C2α/PKB-mediated metabolic signaling IR-B/Shc/ERK-mediated mitogenic signaling,...
Aptamers are single-stranded oligonucleotides that bind to a specific target with high affinity, and widely applied in biomedical diagnostics drug development. However, the use of aptamers has largely been limited simple binders or inhibitors interfere function protein. Here, we show an aptamer can also act as positive allosteric modulator enhances activation receptor by stabilizing binding ligand receptor. We developed aptamer, named IR-A43, which binds insulin receptor, confirmed IR-A43...
Abstract Aptamers are widely used as binders that interact with targets high affinity or inhibitors of the function target molecules. However, they have also been to modulate protein function, which achieve by activating stabilizing its conformation. Here, we report a unique aptamer modulator insulin receptor (IR), IR-A62. Alone, IR-A62 acts biased agonist preferentially induces Y1150 monophosphorylation IR. when administered alongside insulin, shows variable binding cooperativity depending...
Abstract Aminoacyl-tRNA synthetases (ARSs) have evolved to acquire various additional domains. These domains allow ARSs communicate with other cellular proteins in order promote non-translational functions. Vertebrate cytoplasmic isoleucyl-tRNA (IARS1s) an uncharacterized unique domain, UNE-I. Here, we present the crystal structure of chicken IARS1 UNE-I complexed glutamyl-tRNA synthetase 1 (EARS1). consists tandem ubiquitin regulatory X (UBX) that interact a distinct hairpin loop on EARS1...
We present a single-molecule imaging platform that quantitatively explores the spatiotemporal dynamics of individual insulin receptors in living cells. Modified DNA aptamers specifically recognize (IRs) with high affinity were selected through SELEX process. Using quantum dot-labeled aptamers, we successfully imaged and analyzed diffusive motions IRs plasma membranes variety cell lines (HIR, HEK293, HepG2). further explored cholesterol-dependent movement to address whether cholesterol...
Summary Insulin is a key regulator of energy metabolism in peripheral tissues but also functions as growth factor. binding to the insulin receptor (IR) leads autophosphorylation intracellular tyrosine residues, which simultaneously initiates multitude signals and functions. In contrast, some artificial (non-insulin) ligands for IR result biased agonism, selectively activating PI3K/AKT pathway metabolic effects without mitogen-activated protein kinase (MAPK) mitogenic effects. However,...
Aptamers are single‐stranded oligonucleotides (DNA or RNA) and form a unique three‐dimensional (3D) structure based on its sequence. These aptamers have high affinity specificity to target molecule recognize 3D of surface. For this reason, been in the spotlight as universal capture. Especially, can modulate protein allosteric agonist antagonist. However, aptamer‐based enhancer sensitizer (hereafter ‐ sensitizer) has not elucidated. Here, for first time, we show INSR‐A43, which is insulin...
Insulin is a key regulator of energy metabolism in peripheral tissues but also functions as growth factor. binding to the insulin receptor (IR) leads autophosphorylation intracellular tyrosine residues, which simultaneously initiates multitude signals and functions. In contrast, some artificial (non‐insulin) ligands for IR result biased agonism, selectively activating PI3K/AKT pathway metabolic effects without mitogen‐activated protein kinase (MAPK) mitogenic effects. However, precise...