A5031525806- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Amyotrophic Lateral Sclerosis Research
- Ferroptosis and cancer prognosis
- Peptidase Inhibition and Analysis
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Gene expression and cancer classification
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
- Photosynthetic Processes and Mechanisms
- Cancer-related Molecular Pathways
- Click Chemistry and Applications
- Genetic Neurodegenerative Diseases
- MicroRNA in disease regulation
- Nuclear Structure and Function
- Neurogenetic and Muscular Disorders Research
- Trace Elements in Health
- Chemical Synthesis and Analysis
- Muscle Physiology and Disorders
Syracuse University
2016-2025
Instituto Nacional de Enfermedades Neoplásicas
2014-2024
Universidad Nacional José Faustino Sánchez Carrión
2024
Universidad Científica del Sur
2024
Hospital Universitario La Paz
2023
Hospital Nacional Cayetano Heredia
2021
Instituto Nacional de Salud
2021
Fanconi Anemia Research Fund
2020
Federation University
2020
University of Maryland, College Park
2010-2017
Internal ionizable groups in proteins are relatively rare but they essential for catalysis and energy transduction. To examine molecular determinants of their unusual functionally important properties, we engineered 25 variants staphylococcal nuclease with lysine residues at internal positions. Nineteen the Lys have depressed pK(a) values, some as low 5.3, 20 titrate without triggering any detectable conformational reorganization. Apparently, simply by being buried protein interior, these...
The cytoskeleton is a complex network of interconnected biopolymers consisting actin filaments, microtubules, and intermediate filaments. These work in concert to transmit cell-generated forces the extracellular matrix required for cell motility, wound healing, tissue maintenance. While we know are driven by actomyosin contractility balanced microtubule resistance, effect filaments on cellular unclear. Using combination theoretical modeling experiments, show that vimentin tune stress...
Charges are inherently incompatible with hydrophobic environments. Presumably for this reason, ionizable residues usually excluded from the interior of proteins and found instead at surface, where they can interact bulk water. Paradoxically, groups buried in play essential roles, especially biological energy transduction. To examine unusual properties internal we measured p K a glutamic acid 25 positions stable form staphylococcal nuclease. Two Glu titrated normal near 4.5; other 23 elevated...
Abstract Prior computational studies of the acid‐unfolding behavior staphylococcal nuclease (SNase) suggest that p K a values its carboxylic groups are difficult to reproduce with electrostatics calculations continuum methods. To examine molecular determinants in SNase, all 20 Asp and Glu residues were measured multidimensional multinuclear NMR spectroscopy an acid insensitive variant SNase. The crystal structure protein was obtained describe microenvironments groups. Fourteen titrate...
Structural analysis of proteins and nucleic acids is complicated by their inherent flexibility, conferred, for example, linkers between contiguous domains. Therefore, the macromolecule needs to be represented an ensemble conformations instead a single conformation. Determining this challenging because experimental data are convoluted average contributions from multiple conformations. As number degrees freedom generally greatly exceeds independent observables, directly deconvolving into...
UBQLN2 450–624 oligomerizes and undergoes temperature-responsive liquid–liquid phase transitions following a closed-loop temperature–concentration diagram. We recently showed that disease-linked mutations to impart highly varying effects its behavior, ranging from little change significant decrease of saturation concentration formation gels aggregates. However, how single lead these properties is unknown. Here, we use as model system study the sequence determinants separation. hypothesized...
Ubiquitin‐binding shuttle UBQLN2 mediates crosstalk between proteasomal degradation and autophagy, likely via interactions with K48‐ K63‐linked polyubiquitin chains, respectively. comprises self‐associating regions that drive its homotypic liquid–liquid phase separation (LLPS). Specific one of these ubiquitin inhibit LLPS. Here, we show that, unlike ubiquitin, the effects multivalent chains on LLPS are highly dependent chain types. Specifically, K11‐Ub4 K48‐Ub4 generally LLPS, whereas...
Internal ionizable groups are quite rare in water-soluble globular proteins. Presumably, this reflects the incompatibility between charges and hydrophobic environment protein interior. Here we show that proteins can have an inherently high tolerance for internal groups. The 25 positions staphylococcal nuclease were substituted one at a time with Lys, Glu, or Asp without abolishing enzymatic activity detectable changes conformation of protein. Similar results substitutions 6 randomly chosen...
Physical mapping data were combined with public draft and finished sequences to derive subtelomeric sequence assemblies for each of the 41 genetically distinct human telomere regions. Sequence gaps that remain on reference telomeres are generally small,well-defined,and most part,restricted regions directly adjacent terminal (TTAGGG)n tract. Of 20.66 Mb DNA analyzed, 3.01 repeat (Srpt),and an additional 2.11 segmental duplications. The enriched >25-fold in short,internal (TTAGGG)n-like...
Polymeric chains made of a small protein ubiquitin act as molecular signals regulating variety cellular processes controlling essentially all aspects eukaryotic biology. Uncovering the mechanisms that allow differently linked polyubiquitin to serve distinct requires ability make these with native connectivity, defined length, linkage composition, and in sufficient quantities. This, however, has been major impediment field. Here, we present robust, efficient, widely accessible method for...
The ubiquitin-adaptor protein UBQLN2 promotes degradation of several aggregate-prone proteins implicated in neurodegenerative diseases. Missense mutations also cause X-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previously we demonstrated that the liquid-like properties molecular assemblies are altered by a specific pathogenic mutation, P506T, propensity to aggregate correlated with neurotoxicity. Here, systematically assess effects multiple, spatially...
Polyubiquitination is a critical protein post-translational modification involved in variety of processes eukaryotic cells. The molecular basis for selective recognition the polyubiquitin signals by cellular receptors determined conformations chains adopt; this has been demonstrated K48- and K63-linked chains. Recent studies so-called non-canonical (linked via K6, K11, K27, K29, or K33) suggest they play important regulatory roles growth, development, immune system pathways, but biophysical...
Ubiquitination is one of the most common posttranslational modifications in eukaryotic cells. Depending on architecture polyubiquitin chains, substrate proteins can meet different cellular fates, but our understanding how chain linkage controls protein fate remains limited. UBL-UBA shuttle proteins, such as UBQLN2, bind to ubiquitinated and proteasome or other quality control machinery elements play a role determination. Under physiological conditions, UBQLN2 forms biomolecular condensates...
Introducción: Distintas capitales europeas han estado unidas por un patrimonio cultural intangible desde el año 500, creando una red de conocimiento que antecede a la world wide web. Objetivos: El estudio busca recuperar educación y comunicación en ciudades albergan monasterios benedictinos, resaltando su papel como refugios espirituales espacios ejercicio del silencio. Metodología: Se analiza uso los diferentes medios para comunicar monasterios. La investigación examina cómo estos ofrecen...
Ubiquitin-binding shuttle proteins are important components of stress-induced biomolecular condensates in cells. Yeast Dsk2 scaffolds proteasome-containing via multivalent interactions with proteasomes and ubiquitinated substrates under azide-induced mitochondrial stress or extended growth conditions. However, the molecular mechanisms underlying how these work unknown. Here, we identify that middle chaperone-binding STI1 domain is main driver self-association phase separation vitro. On a...