A5022554168- Lipid Membrane Structure and Behavior
- Alzheimer's disease research and treatments
- Cellular transport and secretion
- Inflammatory mediators and NSAID effects
- Receptor Mechanisms and Signaling
- Nanocluster Synthesis and Applications
- Protein Structure and Dynamics
- Endoplasmic Reticulum Stress and Disease
- thermodynamics and calorimetric analyses
- Ubiquitin and proteasome pathways
- Eicosanoids and Hypertension Pharmacology
- Metabolomics and Mass Spectrometry Studies
- Field-Flow Fractionation Techniques
- Cholinesterase and Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Spectroscopy Techniques in Biomedical and Chemical Research
- Effects and risks of endocrine disrupting chemicals
- Topological and Geometric Data Analysis
- Click Chemistry and Applications
- DNA and Nucleic Acid Chemistry
- Supramolecular Self-Assembly in Materials
- Alcohol Consumption and Health Effects
- Caveolin-1 and cellular processes
- Phagocytosis and Immune Regulation
University of Illinois Urbana-Champaign
2018-2024
Florida International University
2015
Abstract Formation of amyloid-beta (Aβ) oligomer pores in the membrane neurons has been proposed to explain neurotoxicity Alzheimerʼs disease (AD). Here, we present three-dimensional structure an Aβ formed a mimicking environment, namely Aβ(1-42) tetramer, which comprises six stranded β-sheet core. The two faces core are hydrophobic and surrounded by membrane-mimicking environment while edges hydrophilic solvent-exposed. By increasing concentration sample, octamers also formed, made...
Alzheimer's Disease (AD) is the most common neurodegenerative disease, and efficient therapeutic early diagnostic agents for AD are still lacking. Herein, we report development of a novel amphiphilic compound, LS-4, generated by linking hydrophobic amyloid-binding distyrylbenzene fragment with hydrophilic triazamacrocycle, which dramatically increases binding affinity toward various amyloid β (Aβ) peptide aggregates, especially soluble Aβ oligomers. Moreover, upon administration LS-4 to...
Cyclooxygenase-2 (COX-2) overexpression is prominent in inflammatory diseases, neurodegenerative disorders, and cancer. Directly monitoring COX-2 activity within its native environment poses an exciting approach to account for illuminate the effect of local environments on protein activity. Herein, we report development CoxFluor, first activity-based sensing live cells with confocal microscopy flow cytometry. CoxFluor strategically links a natural substrate dye precursor engage both...
Biological membranes play key roles in cellular compartmentalization, structure, and its signaling pathways. At varying temperatures, individual membrane lipids sample from different configurations, a process that frequently leads to higher-order phase behavior phenomena. Here, we present persistent homology (PH)-based method for quantifying the structural features of bulk lipids, providing local contextual information on lipid tail organization. Our leverages mathematical machinery...
The human body contains endogenous cannabinoids (endocannabinoids) that elicit effects similar to those of Δ9-tetrahydrocanabinol, the principal bioactive component cannabis. endocannabinoid virodhamine (O-AEA) is constitutional isomer well-characterized cardioprotective and anti-inflammatory anandamide (AEA). chemical structures O-AEA AEA contain arachidonic acid (AA) ethanolamine; however, AA in connected ethanolamine via an ester linkage, whereas through amide linkage. involved regulating...
Abstract Cyclooxygenase‐2 (COX‐2) overexpression is prominent in inflammatory diseases, neurodegenerative disorders, and cancer. Directly monitoring COX‐2 activity within its native environment poses an exciting approach to account for illuminate the effect of local environments on protein activity. Herein, we report development CoxFluor, first activity‐based sensing live cells with confocal microscopy flow cytometry. CoxFluor strategically links a natural substrate dye precursor engage both...
ApoB lipoproteins (apo B-Lp) are produced in hepatocytes, and their secretion requires the cargo receptor sortilin. We examined of apo B-Lp-containing very low-density lipoprotein (VLDL), an LDL progenitor. Sortilin also regulates trafficking subtilase PCSK9, which when secreted binds (LDLR), resulting its endocytosis destruction at lysosome. show that site 2 binding compound (cpd984) has multiple effects including (1) enhanced Apo-Lp secretion, (2) increased cellular PCSK9 retention, (3)...
The ability to determine the binding affinity of lipids proteins is an essential part understanding protein-lipid interactions in membrane trafficking, signal transduction and cytoskeletal remodeling. Classic tools for measuring such include surface plasmon resonance (SPR) isothermal titration calorimetry (ITC). While powerful tools, these approaches have setbacks. ITC requires large amounts purified protein as well lipids, which can be costly difficult produce. Furthermore, SPR are very...
DREAM (downstream regulatory element antagonist modulator) is a neuronal calcium sensor that has been shown to modulate gene expression as well be involved in numerous processes. In this report, we show association of calcium-bound calmodulin (CaM) with mediated by short amphipathic amino acid sequence located between residues 29 and 44 on DREAM. The CaM peptide analogous DREAM(29-44) or full-length protein calcium-dependent dissociation constant 136 nM 3.4 μM, respectively. Thermodynamic...
The ability to determine the binding affinity of lipids proteins is an essential part understanding protein-lipid interactions in membrane trafficking, signal transduction and cytoskeletal remodeling. Classic tools for measuring such include surface plasmon resonance (SPR) isothermal titration calorimetry (ITC). While powerful tools, these approaches have setbacks. ITC requires large amounts purified protein as well lipids, which can be costly difficult produce. Furthermore, SPR are very...
The homeostasis of most organelles requires membrane fusion mediated by soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptors (SNAREs). SNAREs undergo cycles activation and deactivation as membranes move through the cycle. At top cycle, inactive cis-SNARE complexes on a single are activated, or primed, hexameric ATPase associated with diverse cellular activities (AAA+) protein, N-ethylmaleimide-sensitive (NSF/Sec18), its co-chaperone α-SNAP/Sec17. Sec18-mediated ATP...
Abstract The formation of amyloid-beta (Aβ) oligomer pores in the membrane neurons has been proposed as means to explain neurotoxicity Alzheimer’s disease (AD). It is therefore critical characterize Aβ samples membrane-mimicking environments. Here we present first three-dimensional structure an formed dodecyl phosphocholine (DPC) micelles, namely Aβ(1-42) tetramer. comprises a β-sheet core made six β-strands, connected by only two β-turns. faces are hydrophobic and surrounded environment. In...
Alzheimer’s Diseases (AD) is the most common neurodegenerative disease, but efficient therapeutic and early diagnosis agents for this neurological disorder are still lacking. <a>Herein, we report development of a novel amphiphilic compound, LS-4, generated linking hydrophobic amyloid fibril-binding fragment with hydrophilic azamacrocycle that can dramatically increase binding affinity towards various β (Aβ) peptide aggregates. The developed compound exhibits uncommon fluorescence...
SUMMARY Eukaryotic homeostasis relies on membrane fusion catalyzed by SNARE proteins. Inactive bundles are re-activated Sec18/NSF driven disassembly to enable a new round of fusion. We previously found that phosphatidic acid (PA) binds Sec18 sequester it from SNAREs. Dephosphorylation PA dissociates the allowing engage complexes. now report induces conformational changes in protomers, while hexameric cannot bind membranes. The association with was shown be sensitive curvature, suggesting...
ABSTRACT Sortilin regulates hepatic exocytosis and endocytosis of ApoB containing lipoproteins (ApoB-Lp) mediates the secretion subtilase PCSK9. To elucidate connections between these pathways, we previously identified a small molecule (cpd984) that binds to non-canonical site on Sortilin. In cells cpd984 augments ApoB-Lp secretion, increases cellular PCSK9 levels, reduces LDLR expression indicative reduced We have shown insulin-induced degradation occurs through Vps34-dependent autophagy....
Biological membranes play key roles in cellular compartmentalization, structure, and its signaling pathways. At varying temperatures, individual membrane lipids sample from different configurations, a process that frequently leads to higher-order phase behavior phenomena. Here we present persistent homology-based method for quantifying the structural features of bulk lipids, providing local contextual information on lipid tail organization. Our leverages mathematical machinery algebraic...