There is a diverse class of peripheral membrane-binding proteins that specifically bind phosphatidylserine (PS), a lipid that signals apoptosis or cell fusion depending on the membrane context of its presentation. PS-receptors are specialized for particular PS-presenting pathways, indicating that they might be sensitive to the membrane context. In this review, we describe a combination of thermodynamic, structural, and computational techniques that can be used to investigate the mechanisms underlying this sensitivity. As an example, we focus on three PS-receptors of the T-cell Immunoglobulin and Mucin containing (TIM) protein family, which we have previously shown to differ in their sensitivity to PS surface density.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290684 | PMC |
http://dx.doi.org/10.1016/j.bbamem.2018.06.010 | DOI Listing |
In p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 (SREBP-2) pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, new strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
State Key Laboratory of Molecular Medicine and Biological Diagnosis and Treatment (Ministry of Industry and Information Technology), Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China.
Uncontrollable cancer cell growth is characterized by the maintenance of cellular homeostasis through the continuous accumulation of misfolded proteins and damaged organelles. This review delineates the roles of two complementary and synergistic degradation systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system, in the degradation of misfolded proteins and damaged organelles for intracellular recycling. We emphasize the interconnected decision-making processes of degradation systems in maintaining cellular homeostasis, such as the biophysical state of substrates, receptor oligomerization potentials (e.
View Article and Find Full Text PDFJ Mol Biol
January 2025
Department of Chemistry and Biochemistry, California State University, San Bernardino, 5500 University Pkwy, San Bernardino, CA 92407, USA. Electronic address:
So far, site-directed alkylation (SDA) studies on transporters in the Major Facilitator Superfamily (MFS) are mostly performed at conditions different from the native cellular environment. In this study, using GFP-based site-directed PEGylation, ligand-induced conformational changes in the lactose permease of Escherichia coli (LacY), were examined in vivo for the first time. Accessibility/reactivity of single-Cys replacements in a Cys-less LacY-eGFP fusion background was tested using methoxy polyethylene glycol-maleimide-5K (mPEG-Mal-5K) in the absence or presence of a ligand, and the band-shift of the fusion upon PEGylation was detected by in-gel fluorescence.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA. Electronic address:
Most adhesion GPCRs undergo autoproteolytic cleavage during receptor biosynthesis, resulting in non-covalently bound N- and C-terminal fragments (NTF and CTF) that remain associated during receptor trafficking to the plasma membrane. While substantial evidence supports increased G protein signaling when just the CTF is expressed, there is an ongoing debate about whether NTF removal is required to initiate signaling in the context of the wild-type receptor. Here, we use adhesion GPCR latrophilin-3 (ADGRL3) as a model receptor to investigate tethered agonist-mediated activation.
View Article and Find Full Text PDFJ Clin Med
January 2025
Department of Cardiovascular & Thoracic Anaesthesia and Critical Care, University Hospital of Martinique, F-97200 Fort-de-France, Martinique, France.
Acute cardiovascular disorders are incriminated in up to 33% of maternal deaths, and the presence of sickle cell anemia (SCA) aggravates the risk of peripartum complications. Herein, we present a 24-year-old Caribbean woman with known SCA who developed a vaso-occlusive crisis at 36 weeks of gestation that required emergency Cesarean section. In the early postpartum period, she experienced fever with rapid onset of acute respiratory distress in the context of COVID-19 infection that required tracheal intubation and mechanical ventilatory support with broad-spectrum antibiotics and blood exchange transfusion.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!