A5062059600- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Census and Population Estimation
- Bioinformatics and Genomic Networks
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Biotin and Related Studies
- RNA Research and Splicing
- Enzyme Structure and Function
- interferon and immune responses
- Genomics and Chromatin Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Inorganic and Organometallic Chemistry
- ATP Synthase and ATPases Research
- Glycosylation and Glycoproteins Research
- Primary Care and Health Outcomes
- Cardiovascular Function and Risk Factors
- Heat shock proteins research
- Prion Diseases and Protein Misfolding
- Data-Driven Disease Surveillance
- thermodynamics and calorimetric analyses
- Healthcare Policy and Management
University of Washington
1999-2025
United States Census Bureau
2016-2024
Seattle University
2020-2023
Utrecht University
2021
European Bioinformatics Institute
2021
Stockholm University
2021
University of Kansas
2021
ETH Zurich
2021
Science for Life Laboratory
2021
Institute for Systems Biology
2001-2020
We present a statistical model to estimate the accuracy of peptide assignments tandem mass (MS/MS) spectra made by database search applications such as SEQUEST. Employing expectation maximization algorithm, analysis learns distinguish correct from incorrect results, computing probabilities that are based upon scores and number tryptic termini peptides. Using SEQUEST results for generated sample known protein components, we demonstrate computed accurate have high power discriminate between...
A statistical model is presented for computing probabilities that proteins are present in a sample on the basis of peptides assigned to tandem mass (MS/MS) spectra acquired from proteolytic digest sample. Peptides correspond more than single protein sequence database apportioned among all corresponding proteins, and minimal list sufficient account observed peptide assignments derived using expectation−maximization algorithm. Using generated 18 purified as well complex H. influenzae...
We have identified and characterized a novel repressor of human beta-interferon (beta-IFN) gene expression. This protein, designated PRDI-BF1, binds specifically to the PRDI element beta-IFN promoter is distinct from previously reported proteins that bind this sequence. PRDI-BF1 an 88-kD protein containing five zinc-finger motifs. Cotransfection experiments in cultured mammalian cells revealed potent PRDI-dependent transcription. blocks virus induction intact synthetic promoters multiple...
Abstract Cellular functions are governed by molecular machines that assemble through protein-protein interactions. Their atomic details critical to studying their mechanisms. However, fewer than 5% of hundreds thousands human protein interactions have been structurally characterized. Here we test the potential and limitations recent progress in deep-learning methods using AlphaFold2 predict structures for 65,484 We show experiments can orthogonally confirm higher-confidence models. identify...
Abstract We have demonstrated the use of per‐methyl esterification peptides for relative quantification proteins between two mixtures and automated de novo sequence derivation on same dataset. Protein comparison were digested to resultant methylated using either d0‐ or d3‐methanol. Methyl converted carboxylic acids, such as are present side chains aspartic glutamic acid well carboxyl terminus, their corresponding methyl esters. The separate d3‐methylated peptide combined mixture subjected...
Several methods have been used to identify peptides that correspond tandem mass spectra. In this work, we describe a data set of low energy spectra generated from control mixture known protein components can be evaluate the accuracy these methods. As an example, were searched by SEQUEST application against human peptide sequence database. The numbers resulting correct and incorrect assignments then determined. We show how sensitivity error rate are affected use various filtering criteria...
The protein kinase inhibitor 2-aminopurine (2AP) blocks the induction of human β-interferon gene by virus or poly(I)-poly(C) at level transcription. This inhibition is specific, since 2AP does not inhibit either hsp 70 heat-shock high temperature metallothionein cadmium dexamethasone. However, block fos and c- myc proto-oncogenes serum growth factors virus, suggesting that a may be involved in regulation these genes, as well gene. different must required for three they are coordinately...
Mitochondrial dysfunction underlies the etiology of a broad spectrum diseases including heart disease, cancer, neurodegenerative diseases, and general aging process. Therapeutics that restore healthy mitochondrial function hold promise for treatment these conditions. The synthetic tetrapeptide, elamipretide (SS-31), improves function, but mechanistic details its pharmacological effects are unknown. Reportedly, SS-31 primarily interacts with phospholipid cardiolipin in inner membrane. Here we...
Abstract Prostate cancer is unusual among neoplasms in that it may be diagnosed at a curable stage through detection of protein serum, the serine protease prostate-specific antigen (PSA). PSA secreted by both normal and neoplastic prostate epithelial cells response to androgenic hormones has found widespread use screening. Because screening controversial due sensitivity specificity issues, efforts continue focus on identification characterization additional markers used for diagnostic...
The eukaryotic transcriptional repressor PRDI-BF1 contains five zinc fingers of the C2H2 type, and protein binds specifically to PRDI, a 14-bp regulatory element beta interferon gene promoter. We have investigated amino acid sequence requirements for specific binding PRDI found that short stretch acids N terminal first finger are necessary sufficient PRDI-specific binding. contribution individual DNA was by inserting them in various combinations into another finger-containing DNA-binding...
Cell-cycle inhibitors, including paclitaxel, are among the most widely used and effective cancer therapies. However, several challenges limit success of drug resistance toxic side effects. Paclitaxel is thought to act primarily by stabilizing microtubules, locking cells in a mitotic state. resulting cytotoxicity tumor shrinkage rates observed cannot be fully explained this mechanism alone. Here we apply quantitative chemical cross-linking with mass spectrometry analysis paclitaxel-treated...
In hypertrophied and failing hearts, fuel metabolism is reprogrammed to increase glucose metabolism, especially glycolysis. This metabolic shift favors biosynthetic function at the expense of ATP production. Mechanisms responsible for switch are poorly understood. We found that inhibitory factor 1 mitochondrial FoF1-ATP synthase (ATPIF1), a protein known inhibit hydrolysis by reverse during ischemia, was significantly upregulated in pathological cardiac hypertrophy induced pressure overload,...
Human beta-interferon gene expression is induced by virus or poly(I).poly(C). This induction due at least in part to an increase the rate of transcription and does not require protein synthesis. A 40-base-pair DNA sequence within promoter, termed interferon regulatory element (IRE), inducible enhancer mouse fibroblasts, both positive negative sequences have been identified this element. In paper we identify three factors that bind specifically two domains IRE. Two these are present nuclear...
There has been considerable recent interest in proteomic analyses of plasma for the purpose discovering biomarkers. Profiling N-linked glycopeptides is a particularly promising method because population glycosites represents proteomes plasma, cell surface, and secreted proteins at very low redundancy provides compelling link between tissue proteomes. Here, we describe UniPep http://www.unipep.org - database human as resource biomarker discovery.
Proteomic approaches to biological research that will prove the most useful and productive require robust, sensitive, reproducible technologies for both qualitative quantitative analysis of complex protein mixtures. Here we applied isotope-coded affinity tag (ICAT) approach profiling, in this case proteins copurified with lipid raft plasma membrane domains isolated from control stimulated Jurkat human T cells. With ICAT approach, cysteine residues two related isolates were covalently labeled...
Lipid rafts were prepared according to standard protocols from Jurkat T cells stimulated via cell receptor/CD28 cross-linking and control (unstimulated) cells. Co-isolating proteins the preparations labeled with isotopically normal (d0) heavy (d8) versions of same isotope-coded affinity tag (ICAT) reagent, respectively. Samples combined, proteolyzed, resultant peptides fractionated cation exchange chromatography. Cysteine-containing (ICAT-labeled) recovered biotin component ICAT reagents by...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPoly(pyridine)ruthenium(II)-photoinduced redox reactions of bipyridinium cations, poly(pyridine)rhodium complexes, and osmium amminesCarol Creutz, Andrew D. Keller, Norman Sutin, Arden P. ZippCite this: J. Am. Chem. Soc. 1982, 104, 13, 3618–3627Publication Date (Print):June 1, 1982Publication History Published online1 May 2002Published inissue 1 June...
Posttranslational modifications of proteins play an important role in biology. For example, phosphorylation is a key component signal transduction all three domains life, and histones can be modified such variety ways that histone code for gene regulation has been proposed. Shotgun proteomics commonly used to identify posttranslational as well chemical from sample processing. However, it favors the detection abundant peptides over repertoire presented, data analysis usually requires advance...