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Discovery of non-retinoid compounds that suppress the pathogenic effects of misfolded rhodopsin in a mouse model of retinitis pigmentosa.
PLoS Biol
January 2025
Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
Pathogenic mutations that cause rhodopsin misfolding lead to a spectrum of currently untreatable blinding diseases collectively termed retinitis pigmentosa. Small molecules to correct rhodopsin misfolding are therefore urgently needed. In this study, we utilized virtual screening to search for drug-like molecules that bind to the orthosteric site of rod opsin and improve its folding and trafficking.
View Article and Find Full Text PDFKifunensine-sensitive ADP-ribosylation factor A1EG69R mutant revealed coordination of protein glycosylation and vesicle transport pathways.
J Exp Bot
January 2025
Vegetable and Fruit Improvement Center and Department of Horticultural Sciences Texas A&M University, College Station, TX 77843, USA.
Complex N-glycans are asparagine (N)-linked branched sugar chains attached to secretory proteins in eukaryotes. They are produced by modification of N-linked oligosaccharide structures in the endoplasmic reticulum (ER) and Golgi apparatus. Complex N-glycans formed in the Golgi apparatus are often assigned specific roles unique to the host organism, with their roles in plants remaining largely unknown.
View Article and Find Full Text PDFIdentification of the role of SNARE proteins in rAAV vector production through interaction with the viral MAAP.
Mol Ther Methods Clin Dev
March 2025
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Adeno-associated virus (AAV) expresses a membrane-associated accessory protein (MAAP), a small nonstructural protein, that facilitates AAV secretion out of the plasma membrane through an association with extracellular vesicles during AAV egress. Here, we investigated the host proteins that interact with AAV2 MAAP (MAAP2) using APEX2-mediated proximity labeling. We identified two SNARE proteins, Syntaxin 7 (STX7) and synaptosome-associated protein 23 (SNAP23), a vesicle (v-)SNARE and a target (t-)SNARE, respectively, that mediate intracellular trafficking of membrane vesicles aand exhibited associations with MAAP2 in HEK293 cells.
View Article and Find Full Text PDFFluorescent Artificial Receptor for Dopamine based on Molecular Recognition-driven Dynamic Covalent Chemistry in a Lipid Nanoreactor.
Angew Chem Int Ed Engl
January 2025
University of Strasbourg, UMR 7213 CNRS, 74, Route du Rhin, 67401, Illkirch-Strasbourg, FRANCE.
Molecular recognition and detection of small bioactive molecules, like neurotransmitters, remain a challenge for chemists, whereas nature found an elegant solution in form of protein receptors. Here, we introduce a concept of a dynamic artificial receptor that synergically combines molecular recognition with dynamic imine bond formation inside a lipid nanoreactor, inducing a fluorescence response. The designed supramolecular system combines a lipophilic recognition ligand derived from a boronic acid, a fluorescent aldehyde based on push-pull styryl pyridine and a phenol-based catalyst.
View Article and Find Full Text PDFLncRNA MANCR is downregulated in non-small cell lung cancer and predicts poor survival.
Discov Oncol
January 2025
Spinal Surgery Department, the Fourth People's Hospital of Jinan, No.50 Normal Road, Tianqiao District, Jinan, 250031, Shandong, China.
Background: It is known that genomic instability contributes to cancer development. Mitotically associated long non-coding RNA (MANCR) has been reported to promote genomic stability, suggesting its involvement in cancers. Therefore, this study was conducted to investigate the role of MANCR in non-small cell lung cancer (NSCLC).
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