A5073515470- Chronic Lymphocytic Leukemia Research
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Immunodeficiency and Autoimmune Disorders
- Protein Kinase Regulation and GTPase Signaling
- Biochemical and Molecular Research
- Chronic Myeloid Leukemia Treatments
- Toxoplasma gondii Research Studies
- Ion Transport and Channel Regulation
- Lymphoma Diagnosis and Treatment
- Eosinophilic Disorders and Syndromes
- RNA Research and Splicing
- RNA regulation and disease
- Cytomegalovirus and herpesvirus research
- Bacteriophages and microbial interactions
- Cancer-related Molecular Pathways
- Clostridium difficile and Clostridium perfringens research
- HIV/AIDS drug development and treatment
- Poxvirus research and outbreaks
- Glycosylation and Glycoproteins Research
- Bacterial Genetics and Biotechnology
- Immune Cell Function and Interaction
- Legionella and Acanthamoeba research
- Bacillus and Francisella bacterial research
- Ion Channels and Receptors
Iowa State University
2019-2024
Northeastern University
2023
Janssen (United States)
2021
Rockefeller University
2015
University of Maryland, College Park
2012
State Street (United States)
2011
National Institute of Allergy and Infectious Diseases
2006-2008
National Institutes of Health
2006-2008
The gaseous phytohormone ethylene C 2 H 4 mediates numerous aspects of growth and development. Genetic analysis has identified a number critical elements in signaling, but how these interact biochemically to transduce the signal from receptor complex at endoplasmic reticulum (ER) membrane transcription factors nucleus is unknown. To close this gap our understanding signaling pathway, challenge been identify target CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) Raf-like protein kinase, as well...
Signaling through the programmed death 1 (PD-1) inhibitory receptor upon binding its ligand, PD-L1, suppresses immune responses against autoantigens and tumors plays an important role in maintenance of peripheral tolerance. Release from PD-1 signaling revives "exhausted" virus-specific T cells chronic viral infections. Here we present crystal structure murine complex with human PD-L1. PD-L1 interact conserved front side their Ig variable (IgV) domains, as do IgV domains antibodies cell...
Many microbial pathogens deliver effector proteins via the type III secretion system into infected host cells. Elucidating function of these effectors is essential for our understanding pathogenesis. Here, we describe biochemical and structural characterization an protein (NleL) from Escherichia coli O157:H7, a widespread pathogen causing severe foodborne diseases. We show that NleL functionally structurally mimics eukaryotic HECT E3 ligases catalyzes formation unanchored polyubiquitin...
In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial "Trojan horses" integrate eukaryotic ubiquitin system has remained mystery. Here we report crystal structures two E3s, Salmonella SopA Escherichia coli NleL, both in complex with human E2 UbcH7. These...
Bruton's tyrosine kinase (BTK) is the target of therapeutic agent, Ibrutinib, that treats chronic lymphocyte leukemia (CLL), mantle cell lymphoma (MCL) and other B malignancies. Ibrutinib a first in class, covalent BTK inhibitor limits B-cell survival proliferation. Designing new inhibitors has been an important objective for advancing development improved agents against cancer autoimmune disorders. Based on success several second-generation irreversible have developed exhibit fewer...
Ubiquitination is a post-translational modification in which one or more 76 amino acid polypeptide ubiquitin molecules are covalently linked to the lysine residues of target proteins. main pathway for protein degradation that governs variety eukaryotic cellular processes, including cell cycle, vesicle trafficking, antigen presentation and signal transduction. Not surprisingly, aberrations system have been implicated pathogenesis many diseases inflammatory neurodegenerative disorders. Recent...
Abstract Acid-sensing ion channels (ASICs) are proton-gated cation critical for neuronal functions. Studies of ASIC1, a major ASIC isoform and proton sensor, have identified acidic pocket, an extracellular region enriched in residues, as key participant channel gating. While binding to this by the venom peptide psalmotoxin modulates gating, molecular structural mechanisms gating modulation small molecules poorly understood. Here, combining functional, crystallographic, computational...
Full-length Bruton’s tyrosine kinase (BTK) has been refractory to structural analysis. The nearest full-length structure of BTK date consists the autoinhibited SH3–SH2–kinase core. Precisely how N-terminal domains (the Pleckstrin homology/Tec homology [PHTH] domain and proline-rich regions [PRR] contain linker) contribute regulation remains unclear. We have produced crystals for first time but despite efforts stabilize state, diffraction data still reveal only core with no electron density...
The Nef protein produced by the viruses HIV-1 and SIV drives efficient viral replication partially inducing constitutive activation of host cell tyrosine kinases, including members Src Tec families. Here, we uncovered mechanism which both enhanced activity family kinase Btk in vitro cells. A mutant that could not bind to SH3 domain kinases activated same extent as did wild-type Nef, demonstrating distinct mechanisms. SH3-SH2 region formed a homodimer requiring CD loop SH2 domain, was...
The possibility of the release smallpox virus into a predominantly nonimmunized population highlights importance understanding poxvirus biology. Poxviruses encode conserved pathway that is required to oxidize disulfide bonds in nascent viral proteins fold reducing environment eukaryotic host cytoplasm. We present structure last enzyme vaccinia pathway, G4, which almost identical virus. G4 catalyzes formation are critical for maturation and cell infection. contains thioredoxin Cys-X-X-Cys...
Full-length BTK has been refractory to structural analysis. The nearest full-length structure of date consists the autoinhibited SH3-SH2-kinase core. Precisely how N-terminal domains (the Pleckstrin homology/Tec homology (PHTH) domain and proline-rich regions (PRR) contain linker) contribute regulation remains unclear. We have produced crystals for first time but despite efforts stabilize state, diffraction data still reveals only core with no electron density visible PHTH-PRR segment....
Full-length Bruton’s tyrosine kinase (BTK) has been refractory to structural analysis. The nearest full-length structure of BTK date consists the autoinhibited SH3–SH2–kinase core. Precisely how N-terminal domains (the Pleckstrin homology/Tec homology [PHTH] domain and proline-rich regions [PRR] contain linker) contribute regulation remains unclear. We have produced crystals for first time but despite efforts stabilize state, diffraction data still reveal only core with no electron density...
Full-length BTK has been refractory to structural analysis. The nearest full-length structure of date consists the autoinhibited SH3-SH2-kinase core. Precisely how N-terminal domains (the Pleckstrin homology/Tec homology (PHTH) domain and proline-rich regions (PRR) contain linker) contribute regulation remains unclear. We have produced crystals for first time but despite efforts stabilize state, diffraction data still reveals only core with no electron density visible PHTH-PRR segment....
Full-length BTK has been refractory to structural analysis. The nearest full-length structure of date consists the autoinhibited SH3-SH2-kinase core. Precisely how N-terminal domains (the Pleckstrin homology/Tec homology (PHTH) domain and proline-rich regions (PRR) contain linker) contribute regulation remains unclear. We have produced crystals for first time but despite efforts stabilize state, diffraction data still reveals only core with no electron density visible PHTH-PRR segment....
Bruton's Tyrosine Kinase (BTK) is a nonreceptor tyrosine kinase that belongs to the TEC family. Mutations in