A5075833672- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Mass Spectrometry Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Carbohydrate Chemistry and Synthesis
- Ubiquitin and proteasome pathways
- Sulfur Compounds in Biology
- Extracellular vesicles in disease
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Monoclonal and Polyclonal Antibodies Research
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Fungal and yeast genetics research
- Neuropeptides and Animal Physiology
- Microtubule and mitosis dynamics
- Bioinformatics and Genomic Networks
- Protist diversity and phylogeny
- Genomics and Phylogenetic Studies
- DNA Repair Mechanisms
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
Indiana University Bloomington
2016-2025
Indiana University
2016-2024
University of California, San Francisco
2006-2017
Bloomington Health Foundation
2016
Friedrich Schiller University Jena
2012
Jena University Hospital
2012
City College of San Francisco
2012
Harvard University
2000-2004
Aberrant protein aggregation is a hallmark of many age-related diseases, yet little known about whether proteins aggregate with age in non-disease setting. Using systematic proteomics approach, we identified several hundred that become more insoluble the multicellular organism Caenorhabditis elegans. These are predicted to be significantly enriched β-sheets, which promote disease aggregation. Strikingly, these highly over-represented aggregates found human neurodegeneration. We examined vivo...
O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic, reversible monosaccharide modifier of serine and threonine residues on intracellular protein domains. Crosstalk between O-GlcNAcylation phosphorylation has been hypothesized. Here, we identified over 1750 16,500 sites from murine synaptosomes, respectively. In total, 135 (7%) all were also found to be phosphorylation. Although many proteins extensively phosphorylated minimally O-GlcNAcylated, O-GlcNAcylated almost always similar or...
<i>O</i>-GlcNAc is a widespread dynamic carbohydrate modification of cytosolic and nuclear proteins with features analogous to phosphorylation. <i>O-</i>GlcNAc acts critically in many cellular processes, including signal transduction, protein degradation, regulation gene expression. However, the study its specific regulatory functions has been limited by difficulties mapping sites modification. We report methods for direct enrichment identification <i>in vivo O-</i>GlcNAc-modified peptides...
The postsynaptic density (PSD) signaling machinery contains proteins with diverse functions. Brain region-specific variations in PSD components mediate distinct physiological responses to synaptic activation. We have developed mass spectrometry-based methods comprehensively compare both relative protein expression and phosphorylation status from present biochemical preparations of density. Using these methods, we determined the 2159 1564 sites murine cortex, midbrain, cerebellum,...
Analysis of the phosphoproteomes and gene interaction networks divergent yeast species defines relative contribution changes in protein phosphorylation pathways to generation phenotypic diversity.
We present the first large scale study characterizing both N- and O-linked glycosylation in a site-specific manner on hundreds of proteins. demonstrate that lectin-affinity fractionation step using wheat germ agglutinin enriches not only peptides carrying intracellular O-GlcNAc, but also those bearing ER/Golgi-derived carbohydrate structures. Liquid chromatography-MS (LC/MS) analysis with high accuracy precursor mass measurements sensitivity ion trap electron-transfer dissociation (ETD) were...
Differences in the ability of opioid drugs to promote regulated endocytosis <i>μ</i>-opioid receptors are related their tendency produce drug tolerance and dependence. Here we show that drug-specific differences receptor internalization determined by a conserved, 10-residue sequence receptor's carboxyl-terminal cytoplasmic tail. Diverse opioids induce phosphorylation at serine (S)375, present middle this sequence, but differ markedly drive higher-order on flanking residues [threonine (T)370,...
Mass spectrometry-based proteomics is a powerful tool for identifying hundreds to thousands of posttranslational modifications in complex mixtures. However, it remains enormously challenging simultaneously assess the intrinsic catalytic efficiencies ( k cat / K M ) these context their natural interactors. Such fundamental enzymological constants are key determining substrate specificity and establishing timing importance cellular signaling. Here, we report use selected reaction monitoring...
While phosphorylation and O-GlcNAc (cytoplasmic nuclear glycosylation) are linked to normal pathological changes in cell states, these post-translational modifications have been difficult analyze proteomic studies. We describe advances beta-elimination / Michael addition-based approaches which allow for mass spectrometry-based identification comparative quantification of O-phosphate or O-GlcNAc-modified peptides, as well cysteine-containing peptides expression analysis. The method (BEMAD)...
Synapses are highly specialized intercellular junctions organized by adhesive and scaffolding molecules that align presynaptic vesicular release with postsynaptic neurotransmitter receptors. The MALS/Veli–CASK–Mint-1 complex of PDZ proteins occurs on both sides the synapse has potential to link transsynaptic adhesion cytoskeleton. In this study, we purified MALS protein from brain found liprin-α as a major component. Liprin organize active zone regulate release. Fittingly, mutant mice...
Partial and full agonists of opioid receptors produce distinct responses by enriching populations phosphorylated receptors.
The retrograde transport of Trk-containing endosomes from the axon to cell body by cytoplasmic dynein is necessary for axonal and neuronal survival. We investigated recruitment signaling in rat embryonic neurons PC12 cells. identified a novel phosphoserine on intermediate chains (ICs), we observed time-dependent neurotrophin-stimulated increase chain phosphorylation this site both types. Pharmacological studies, overexpression constitutively active MAP kinase kinase, an vitro assay with...
Hydrogen sulfide (H2S) is thought to protect bacteria from oxidative stress, but a comprehensive understanding of its function in largely unexplored. In this study, we show that the human pathogen Staphylococcus aureus (S. aureus) harbors significant effector molecules H2S signaling, reactive sulfur species (RSS), as low molecular weight persulfides bacillithiol, coenzyme A, and cysteine, inorganic polysulfide species. We find proteome S-sulfhydration, post-translational modification (PTM)...
Sulfide was used as an electron donor early in the evolution of photosynthesis, with many extant photosynthetic bacteria still capable using sulfur compounds such hydrogen sulfide (H
Acinetobacter baumannii is an important nosocomial pathogen capable of causing wound infections, pneumonia, and bacteremia. During infection, A. must acquire Zn to survive colonize the host. Vertebrates have evolved mechanisms sequester from invading pathogens by a process termed nutritional immunity. One most upregulated genes during starvation encodes putative cell wall-modifying enzyme which we named ZrlA. We found that inactivation zrlA diminished growth starvation. Additionally, this...
Low-complexity "prion-like" domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these have been linked to specific neurodegenerative diseases. Although their aggregation neurodegeneration has extensively characterized, it remains unknown how process aging disturbs RBP dynamics. We show that a wide variety granule components, including stress proteins, become highly insoluble with age C. elegans and reduced insulin/insulin-like...
Adaptation to endogenous oxidative stress is an integral aspect of Streptococcus pneumoniae colonization and virulence. In this work, we identify key transcriptomic proteomic features the pneumococcal response. The thiol peroxidase TpxD plays a critical role in adaptation H 2 O serves limit protein sulfenylation glycolytic, capsule, nucleotide biosynthesis enzymes S. .
The Pseudomonas syringae effector protein AvrRpm1 activates the Arabidopsis intracellular innate immune receptor RPM1 via modification of a second protein, RIN4. Prior work has shown that induces phosphorylation AtRIN4, but homology modeling indicated may be an ADP-ribosyl transferase. Here we show ADP-ribosylation RIN4 proteins from both and soybean within two highly conserved nitrate-induced (NOI) domains. It also ADP-ribosylates at least ten additional NOI domain-containing proteins....