A5076771058- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Genetic Syndromes and Imprinting
- Parathyroid Disorders and Treatments
- Nuclear Structure and Function
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic function and diabetes
- Mitochondrial Function and Pathology
- Cell Image Analysis Techniques
- Lysosomal Storage Disorders Research
- Lipid metabolism and biosynthesis
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Atherosclerosis and Cardiovascular Diseases
- Interdisciplinary Research and Collaboration
- Lipid Membrane Structure and Behavior
- Wnt/β-catenin signaling in development and cancer
- Climate Change Communication and Perception
- 3D Printing in Biomedical Research
- Skin and Cellular Biology Research
- Advanced Proteomics Techniques and Applications
- Microfluidic and Bio-sensing Technologies
Enzo Life Sciences (United States)
2022-2024
Institute for Atomic and Molecular Physics
2012-2022
National Heart Lung and Blood Institute
2021
Abstract Human papillomavirus (HPV) is a significant contributor to the global cancer burden, and its carcinogenic activity facilitated in part by HPV early protein 6 (E6), which interacts with E3-ligase E6AP, also known as UBE3A, promote degradation of tumor suppressor, p53. In this study, we present single-particle cryoEM structure full-length E6AP complex HPV16 E6 (16E6) p53, determined at resolution ~3.3 Å. Our reveals extensive protein-protein interactions between 16E6 explaining their...
To power dynamic processes in cells, the actin and microtubule cytoskeletons organize into complex structures. Although it is known that cytoskeletal coordination vital for cell function, mechanisms by which cross-linking proteins coordinate activities remain poorly understood. In particular, unknown how distinct mechanical properties of different architectures modulate outcome actin–microtubule interactions. address this question, we engineered protein TipAct, links growing ends via...
Microtubule-dependent organization of membranous organelles occurs through motor-based pulling and by coupling microtubule dynamics to membrane remodeling. For example, tubules endoplasmic reticulum (ER) can be extended kinesin- dynein-mediated transport the association with tips dynamic microtubules. The binding between ER growing plus ends requires End Binding (EB) proteins transmembrane protein STIM1, which form a tip-attachment complex (TAC), but it is unknown whether these are...
SignificanceComplex cellular processes such as cell migration require coordinated remodeling of both the actin and microtubule cytoskeleton. The two networks for instance exert forces on each other via active motor proteins. Here we show that, surprisingly, coupling passive cross-linkers can also result in force generation. We specifically study transport filaments by growing ends. cell-free reconstitution experiments, computer simulations, theoretical modeling that this is driven affinity...
Abstract Cellular organelles undergo constant morphological changes and dynamic interactions that are fundamental to cell homeostasis, stress responses disease progression. Despite their importance, quantifying organelle morphology motility remains challenging due complex architectures, rapid movements the technical limitations of existing analysis tools. Here we introduce Nellie, an automated unbiased pipeline for segmentation, tracking feature extraction diverse intracellular structures....
Abstract α‐Klotho, an aging‐related protein found in the kidney, parathyroid gland, and choroid plexus, acts as essential co‐receptor with fibroblast growth factor 23 receptor complex to regulate serum phosphate vitamin D levels. Decreased levels of α‐Klotho are a hallmark age‐associated diseases. Detecting or labeling biological milieu has long been challenge, however, hampering understanding its role. Here, we developed branched peptides by single‐shot parallel automated fast‐flow...
The analysis of dynamic organelles remains a formidable challenge, though key to understanding biological processes. We introduce Nellie, an automated and unbiased pipeline for segmentation, tracking, feature extraction diverse intracellular structures. Nellie adapts image metadata, eliminating user input. Nellie's preprocessing enhances structural contrast on multiple scales allowing robust hierarchical segmentation sub-organellar regions. Internal motion capture markers are generated...
Protein–protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides well suited to target PPIs, which typically present with large surface areas lacking distinct features deep binding pockets. To improve these topologies advance the development of PPI-focused therapeutics, potential ligands can be equipped electrophilic groups enable through covalent mechanisms action. We report a strategy termed electrophile scanning identify reactivity hotspots known...
Cancer cells migrating in confined microenvironments exhibit plasticity of migration modes. Confinement contractile a nonadhesive environment drives "leader bleb-based migration" (LBBM), morphologically characterized by long bleb that points the direction movement separated from cell body neck. Although undergoing LBBM have been visualized within tumors, organization organelles and actin regulatory proteins mediating is unknown. We analyzed localization fluorescent organelle-specific markers...
Protein–protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides well suited to target PPIs, which typically present with large surface areas lacking distinct features deep binding pockets. To improve these topologies by PPI-focused therapeutics advance their development, potential ligands can be equipped electrophilic groups enable through covalent mechanisms of action. We report a strategy termed electrophile scanning identify reactivity hotspots known...
Mitochondrial networks exhibit remarkable dynamics that are driven in part by fission and fusion events. However, there other reorganizations of the network do not involve fusion. One such exception is elusive, beads-on-a-string morphological transition mitochondria. During transitions, cylindrical tubes mitochondrial membrane transiently undergo shape changes to a string pearls connected along thin tubes. These have been anecdotally observed many contexts given disparate explanations. Here...
Abstract α‐Klotho, an aging‐related protein found in the kidney, parathyroid gland, and choroid plexus, acts as essential co‐receptor with fibroblast growth factor 23 receptor complex to regulate serum phosphate vitamin D levels. Decreased levels of α‐Klotho are a hallmark age‐associated diseases. Detecting or labeling biological milieu has long been challenge, however, hampering understanding its role. Here, we developed branched peptides by single‐shot parallel automated fast‐flow...
Systemic lupus erythematosus is a common autoimmune inflammatory disease which associated with increases in autoantibodies and immune complexes that deposit the kidney. The MRL-lpr mouse model used for study of complex glomerulonephritis but very little known about plasma proteome changes this model. We performed in-depth quantitative profiling on control (strain MpJ) mice to investigate proteome, immunoglobulins their glycoproteome as well protein complexes. Methodologies included...
The kidney, parathyroid gland, and choroid plexus express the aging-related transmembrane protein α-Klotho, a coreceptor of fibroblast growth factor 23 (FGF23) receptor complex. Reduced α-Klotho levels are correlated with chronic kidney disease other age-related diseases, wherein they released from membranes into circulation. Klotho's potential physiological action as hormone is current scientific interest. Part challenges associated advancing these studies, however, has been long-standing...
One of the main hallmarks aging is aging-associated inflammation, also known as inflammaging. In this study, by comparing plasma and kidney proteome profiling young old mice using LC–MS profiling, we discovered that immunoglobulins are proteins exhibit highest increase with age. This observation seems to have been disregarded because conventional experiments typically overlook expression high-abundance or employ depletion methods remove them before analysis. We show will likely be a useful...
Protein aggregation increases during aging and is a pathological hallmark of many age-related diseases. homeostasis (proteostasis) depends on core network factors directly influencing protein production, folding, trafficking, degradation. Cellular proteostasis also the overall composition proteome numerous environmental variables. Modulating this cellular state can influence stability multiple endogenous proteins, yet contributing to remain incompletely characterized. Here, we performed...
Protein aggregation increases during aging and is a pathological hallmark of many age-related diseases. homeostasis (proteostasis) depends on core network factors directly influencing protein production, folding, trafficking, degradation. Cellular proteostasis also the overall composition proteome numerous environmental variables. Modulating this cellular state can influence stability multiple endogenous proteins, yet contributing to remain incompletely characterized. Here, we performed...
Abstract α-Klotho is a protein associated with aging that expressed in the kidney, parathyroid gland, and choroid plexus. As transmembrane protein, it acts as an essential co-receptor fibroblast growth factor 23 receptor complex to regulate serum phosphate vitamin D levels. has extracellular domain can be cleaved, released circulated blood stream soluble form. Decreased levels of are indication chronic kidney disease other age-associated diseases. Detecting or labeling longstanding challenge...