A5026178097- Ubiquitin and proteasome pathways
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Autophagy in Disease and Therapy
- Protein Degradation and Inhibitors
- Ferroptosis and cancer prognosis
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
- Synthesis and Properties of Aromatic Compounds
- Plant nutrient uptake and metabolism
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Sphingolipid Metabolism and Signaling
- Peptidase Inhibition and Analysis
- Advanced biosensing and bioanalysis techniques
- Photochromic and Fluorescence Chemistry
- Epigenetics and DNA Methylation
- Molecular spectroscopy and chirality
- Cystic Fibrosis Research Advances
- Trace Elements in Health
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Lipid Membrane Structure and Behavior
- Mitochondrial Function and Pathology
- Plant biochemistry and biosynthesis
University of California, Berkeley
2021-2024
Chan Zuckerberg Initiative (United States)
2023
University of Massachusetts Amherst
2017-2022
San Jose State University
2013-2019
University of Wisconsin–Madison
2016
University of Manitoba
2013-2015
Guru Nanak Dev University
1983
Chiral thiol capping ligands l- and d-cysteines induced modular chiroptical properties in achiral cadmium selenide quantum dots (CdSe QDs). Cys-CdSe prepared from oleic acid capped CdSe by postsynthetic ligand exchange displayed size-dependent electronic circular dichroism (CD) circularly polarized luminescence (CPL). Opposite CPL signals were measured for the QDs with d- l-cysteine. The CD profile anisotropy varied size of nanocrystals largest observed nanoparticles 4.4 nm. Magic angle...
Abstract Electronic circular dichroism and circularly polarized luminescence acid/base switching activity has been demonstrated in helicene‐bipyridine proligand 1 a its “rollover” cycloplatinated derivative 2 . Whereas displays strong bathochromic shift (>160 nm) of the nonpolarized upon protonation, complex slightly stronger emission. This strikingly different behavior between singlet emission organic helicene triplet organometallic rationalized by using quantum‐chemical calculations....
Enantiopure mono-cycloplatinated-[8]helicene and bis-cycloplatinated-[6]helicene derivatives were prepared through column chromatography combined with crystallization of diastereomeric complexes using a chiral ancillary sulfoxide ligand. The UV-visible spectra, circular dichroism, molar rotations, (circularly polarized) luminescence activity these new helical have been examined in detail analysed the help first-principles quantum-chemical calculations.
Despite the key roles of perilipin-2 (PLIN2) in governing lipid droplet (LD) metabolism, mechanisms that regulate PLIN2 levels remain incompletely understood. Here, we leverage a set genome-edited human reporter cell lines series CRISPR-Cas9 loss-of-function screens, identifying genetic modifiers influence expression and post-translational stability under different metabolic conditions types. These regulators include canonical genes control metabolism as well involved ubiquitination,...
Ubiquitin (Ub) has a broad functional range that been ascribed to the formation of an array polymeric ubiquitin chains. Understanding precise roles chains, however, is difficult due their complex chain topologies. Branched chains are particularly challenging, as multiple modifications on single preclude use standard bottom-up proteomic approaches. Developing methods overcome these challenges crucial considering evidence suggesting branched regulate stability proteins. In this study, we...
Abstract Imbalances in lipid storage and secretion lead to the accumulation of hepatocyte droplets (LDs) (i.e., hepatic steatosis). Our understanding mechanisms that govern channeling neutral lipids towards cytosolic LDs or secreted lipoproteins remains incomplete. Here, we performed a series CRISPR-Cas9 screens under different metabolic states uncover flux. Clustering chemical-genetic interactions identified CLIC-like chloride channel 1 (CLCC1) as critical regulator secretion. Loss CLCC1...
Degradation by the 26 S proteasome is an intricately regulated process fine tuned precise nature of ubiquitin modifications attached to a protein substrate. By debranching chains composed K48 linkages, proteasome-associated C-terminal hydrolase UCHL5/UCH37 serves as positive regulator degradation. How UCH37 achieves specificity for unclear. Here, we use combination hydrogen-deuterium mass spectrometry, chemical crosslinking, small-angle X-ray scattering, nuclear magnetic resonance (NMR),...
Abstract Background Sucrose transporters (SUTs) play important roles in regulating the translocation of assimilates from source to sink tissues. Identification and characterization new SUT s economically crops such as wheat provide insights into their role determining seed yield. To date, however, only one has been reported functionally characterized. The present study reports isolation a , designated TaSUT2 its homeologues ( TaSUT2A TaSUT2B TaSUT2D ) hexaploid Triticum aestivum L.). Results...
Misregulation of the E3 ubiquitin ligase Parkin and kinase PINK1 underlie both inherited idiopathic Parkinson's disease-associated neurodegeneration. work together to catalyze assembly chains on substrates located outer mitochondrial membrane facilitate autophagic removal damaged mitochondria through a process termed mitophagy. Quantitative measurements Parkin-mediated chain assembly, in vitro mitochondria, have revealed that are composed Lys6, Lys11, Lys48, Lys63 linkages. The combinatorial...
Deregulation of the HECT-type ubiquitin ligase E6AP (UBE3A) is implicated in human papilloma virus-induced cervical tumorigenesis and several neurodevelopmental disorders. Yet structural underpinnings activity specificity this crucial are incompletely understood. Here, we unravel determinants recognition by catalytic domain assign them to particular steps cycle. We identify a functionally critical interface that specifically required during initial formation thioester-linked intermediate...
Lipid droplets are endoplasmic reticulum-derived neutral lipid storage organelles that play critical roles in cellular and energy homeostasis. Here, we present a protocol for the identification of high-confidence droplet proteomes cell culture model. This approach overcomes limitations associated with standard biochemical fractionation techniques, employing an engineered ascorbate peroxidase (APEX2) to biotinylate endogenous proteins living cells subsequent purification by proteomics. For...
Active-site directed probes are powerful tools for studying the ubiquitin conjugation and deconjugation machinery. Branched chains have emerged as important proteasome-targeting signals aggregation-prone proteins cell cycle regulators. By implementing a new synthetic strategy electrophilic warhead, we herein report on generation reactivity of series branched triubiquitin active-site probes. These can be used to dissect molecular basis chain assembly disassembly.
Information embedded in different ubiquitin chains is transduced by proteins with ubiquitin-binding domains (UBDs) and erased a set of hydrolytic enzymes referred to as deubiquitinases (DUBs). Understanding the selectivity UBDs DUBs necessary for decoding functions chains. Critical these efforts access chemically defined bearing site-specific fluorescent labels. One approach toward constructing such molecules involves peptide ligation sortase (SrtA), bacterial transpeptidase responsible...
Over 80% of people with cystic fibrosis (CF) carry the F508del mutation in transmembrane conductance regulator (CFTR), a chloride ion channel at apical plasma membrane (PM) epithelial cells. impairs CFTR folding causing it to be destroyed by endoplasmic reticulum associated degradation (ERAD). Small-molecule correctors, which act as pharmacological chaperones divert CFTR-F508del from ERAD, are primary strategy for treating CF, yet corrector development continues only rudimentary...
ABSTRACT Ferroptosis is a regulated form of cell death associated with the iron-dependent accumulation lipid peroxides. Inducing ferroptosis promising approach to treat therapy resistant cancer. suppressor protein 1 (FSP1) promotes resistance in cancer by generating antioxidant coenzyme Q10 (CoQ). Despite important role FSP1, few molecular tools exist that target CoQ-FSP1 pathway. Exploiting series chemical screens, we identify several structurally diverse FSP1 inhibitors. The most potent...
Abstract This study investigates the significantly different luminescent and chiroptical properties of tetracycline (TC) when coordinated to Eu(III). The approach involves understanding 1) speciation TC 2) conformation species formed between Eu(III) in a ratio 1 : dimethylformamide (DMF) solution as function pH value. By identifying conformational changes various species, results from this explain information on local microenvironment about metal center. In particular, 5 D 0 ← 7 F laser...
SUMMARY The linkage, length, and architecture of ubiquitin (Ub) chains are all important variables in providing tight control over many biological paradigms. There clear roles for branched architectures regulating proteasome-mediated degradation, however the proteins that selectively recognize process these atypical unknown. Here, using synthetic enzyme-derived along with intact mass spectrometry, we report UCH37/UCHL5, a proteasome-associated deubiquitinase, exclusively cleaves K48 chains....
ABSTRACT Ferroptosis is a regulated, iron-dependent form of necrosis that triggered by the accumulation oxidatively damaged phospholipids 1–3 . Glutathione peroxidase 4 (GPX4) prevents ferroptosis converting phospholipid hydroperoxides into non-toxic lipid alcohols 4, 5 has been implicated in pathology several degenerative conditions and inhibiting GPX4 activity emerged as therapeutic strategy to induce cancer cell death 1, 2 However, many lines are resistant inhibition 6 , mechanisms...
ABSTRACT Lipid droplets (LDs) are lipid storage organelles that consist of a central core neutral lipids surrounded by phospholipid monolayer decorated with unique set integral and peripheral proteins. Invariably, at least one member the perilipin family proteins (PLIN1-5) associates LDs in all cell types. Despite key roles PLIN2 governing hepatic metabolism, mechanisms regulate levels remain incompletely understood. Here, we develop genome-edited reporter lines facilitate analysis genes LD...