A5006466249- Electron Spin Resonance Studies
- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Nitric Oxide and Endothelin Effects
- Drug Transport and Resistance Mechanisms
- Neuroscience and Neuropharmacology Research
- Mass Spectrometry Techniques and Applications
- DNA and Nucleic Acid Chemistry
- Lanthanide and Transition Metal Complexes
- Computational Drug Discovery Methods
- Advanced NMR Techniques and Applications
- Nicotinic Acetylcholine Receptors Study
- Protein Kinase Regulation and GTPase Signaling
- Photosynthetic Processes and Mechanisms
- Antimicrobial Resistance in Staphylococcus
- RNA and protein synthesis mechanisms
- Legume Nitrogen Fixing Symbiosis
- Ion channel regulation and function
- Salmonella and Campylobacter epidemiology
- Advanced MRI Techniques and Applications
- Lipid Membrane Structure and Behavior
- Hemoglobin structure and function
- Plant Micronutrient Interactions and Effects
Medical College of Wisconsin
2015-2025
Ball State University
2016
Vanderbilt University
2013
Park University
2011
Doheny Eye Institute
2006
University of California, Los Angeles
2001-2006
University of Oregon
2002
Leipzig University
1998-1999
University of Denver
1998
Arrestins regulate signaling and trafficking of G protein-coupled receptors by virtue their preferential binding to the phosphorylated active form receptor. To identify sites in arrestin involved receptor interaction, a nitroxide-containing side chain was introduced at each 28 different positions visual arrestin, dynamics used monitor interaction with forms its cognate receptor, rhodopsin. At physiological concentrations, associates both inactive dark rhodopsin (P-Rh) light-activated...
Arrestins bind active phosphorylated forms of G protein-coupled receptors, terminating protein activation, orchestrating receptor trafficking, and redirecting signaling to alternative pathways. Visual arrestin-1 preferentially binds rhodopsin, whereas the two non-visual arrestins interact with hundreds subtypes. Here we show that an extensive surface on concave side both arrestin-2 domains is involved in binding. We also identified a small number residues binding N- C-domains largely...
A unique aspect of arrestin-3 is its ability to support both receptor-dependent and receptor-independent signaling. Here, we show that inositol hexakisphosphate (IP6) a non-receptor activator report the structure IP6-activated at 2.4-Å resolution. exhibits an inter-domain twist displaced C-tail, hallmarks active arrestin. IP6 binds arrestin phosphate sensor, stabilized by trimerization. Analysis trimerization surface, which also receptor-binding suggests feature called finger loop as key...
Polymyxins are antibiotics used in the last line of defense to combat multidrug-resistant infections by Gram-negative bacteria. Polymyxin resistance arises through charge modification bacterial outer membrane with attachment cationic sugar 4-amino-4-deoxy-l-arabinose lipid A, a reaction catalyzed integral lipid-to-lipid glycosyltransferase 4-amino-4-deoxy-L-arabinose transferase (ArnT). Here, we report crystal structures ArnT from Cupriavidus metallidurans, alone and complex carrier...
The maltose transporter MalFGK 2 of Escherichia coli is a member the ATP-binding cassette superfamily. A periplasmic maltose-binding protein (MBP) delivers to and stimulates its ATPase activity. Site-directed spin labeling EPR spectroscopy was used study opening closing nucleotide-binding interface during catalytic cycle. In intact transporter, closure coincides not just with binding ATP, as seen isolated domains, but requires both MBP implying that activity by promoting interface. After ATP...
The non-visual arrestins, arrestin-2 and arrestin-3, belong to a small family of multifunctional cytosolic proteins. Non-visual arrestins interact with hundreds G protein-coupled receptors (GPCRs) regulate GPCR desensitization by binding active phosphorylated GPCRs uncoupling them from heterotrimeric Recently, have been shown mediate protein-independent signaling serving as adaptors scaffolds that assemble multiprotein complexes. By recruiting various partners, including trafficking...
Recently we found that visual arrestin binds microtubules and this interaction plays an important role in localization photoreceptor cells. Here use site-directed mutagenesis spin labeling to explore the molecular mechanism of novel regulatory interaction. The microtubule binding site maps concave sides two domains, overlapping with rhodopsin site, which makes interactions mutually exclusive. Arrestin is enhanced by several "activating mutations" involves multiple positive charges...
The maltose transport complex of Escherichia coli, a member the ATP-binding cassette superfamily, mediates high affinity uptake at expense ATP. membrane-associated transporter consists two transmembrane subunits, MalF and MalG, copies cytoplasmic subunit, MalK. Maltose-binding protein (MBP), soluble periplasmic protein, delivers to MalFGK(2) stimulates hydrolysis by transporter. Site-directed spin labeling electron paramagnetic resonance spectroscopy is used monitor binding MBP...
Gram-negative bacteria such as Escherichia coli have an inner membrane and asymmetric outer (OM) that together protect the cytoplasm act a highly selective permeability barrier. Lipopolysaccharide (LPS) is major component of leaflet OM essential for survival nearly all bacteria. Recent advances in understanding proteins involved transport LPS across periplasm into include identification seven suggested to comprise (Lpt) system. Crystal structures periplasmic Lpt protein LptA recently been...
Pentameric ligand-gated ion channels (pLGICs) are neurotransmitter-activated receptors that mediate fast synaptic transmission. In pLGICs, binding of agonist to the extracellular domain triggers a structural rearrangement leads opening an ion-conducting pore in transmembrane and, continued presence neurotransmitter, desensitize (close). The flexible loops each subunit connect (loops 2, 7, and 9) channel (M2–M3 loop) essential for coupling ligand gating. Comparing crystal structures two...
Summary MalFGK 2 is an ATP ‐binding cassette ( ABC ) transporter that mediates the uptake of maltose/maltodextrins into E scherichia coli . A periplasmic maltose‐binding protein MBP delivers maltose to transmembrane subunits MalFG and stimulates ase activity cytoplasmic nucleotide‐binding MalK dimer). This ‐stimulated independent for purified in detergent micelles. However, when reconstituted membrane bilayers, only liganded form efficiently its activity. To investigate mechanism...
Abstract Membrane interactions play a crucial role in regulating arrestin activation and its binding to phosphorylated G protein-coupled receptors (GPCRs). Here, we utilize vitro biophysical approaches cell-based fluorescence intensity fluctuation analysis systematically compare the membrane-binding properties of two highly conserved subtypes, arrestin-2 arrestin-3, under basal stimulated conditions. Our findings reveal that selectively engages PI(4,5)P 2 -containing nanodiscs via C-edge,...