A5044482648- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Microbial Natural Products and Biosynthesis
- Herpesvirus Infections and Treatments
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Legionella and Acanthamoeba research
- Pneumonia and Respiratory Infections
- Biofuel production and bioconversion
- Animal Virus Infections Studies
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- interferon and immune responses
- Cellular Mechanics and Interactions
- Catalysis for Biomass Conversion
- Asymmetric Hydrogenation and Catalysis
- Melanoma and MAPK Pathways
- Enzyme Structure and Function
- Viral gastroenteritis research and epidemiology
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Immune Response and Inflammation
- Respiratory viral infections research
The University of Texas at Austin
2021-2024
University of San Diego
2018-2020
SARS-CoV-2 infection is controlled by the opening of spike protein receptor binding domain (RBD), which transitions from a glycan-shielded 'down' to an exposed 'up' state bind human angiotensin-converting enzyme 2 and infect cells. While snapshots states have been obtained cryo-electron microscopy tomagraphy, details RBD-opening transition evade experimental characterization. Here over 130 µs weighted ensemble simulations fully glycosylated ectodomain allow us characterize more than 300...
Abstract CRISPR–Cas9 as a programmable genome editing tool is hindered by off-target DNA cleavage 1–4 , and the underlying mechanisms which Cas9 recognizes mismatches are poorly understood 5–7 . Although variants with greater discrimination against have been designed 8–10 these suffer from substantially reduced rates of on-target 5,11 Here we used kinetics-guided cryo-electron microscopy to determine structure at different stages mismatch cleavage. We observed distinct, linear conformation...
Abstract SARS-CoV-2 infection is controlled by the opening of spike protein receptor binding domain (RBD), which transitions from a glycan-shielded “down” to an exposed “up” state in order bind human ACE2 and infect cells. While snapshots states have been obtained cryoEM cryoET, details RBD transition evade experimental characterization. Here, over 130 μs weighted ensemble (WE) simulations fully glycosylated ectodomain allow us characterize more than 300 continuous, kinetically unbiased...
Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize in its metastable prefusion conformation. One variant two engineered interprotomer disulfide bonds cavity-filling (gB-C7), displayed increased expression...
Abstract Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no has been FDA-approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize in its metastable prefusion conformation. One variant two engineered interprotomer disulfide bonds cavity-filling (gB-C7), displayed increased expression...
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants, infecting all children by age 5. RSV also causes substantial morbidity mortality older adults, a vaccine for adults based on prefusion-stabilized form viral F glycoprotein was recently approved FDA. Here, we investigate set antibodies that belong to same public clonotype were isolated from individuals vaccinated with protein. Our results reveal these are highly potent recognize previously...
The widespread use of CRISPR/Cas9 as a programmable genome editing tool has been hindered by off-target DNA cleavage (Cong et al., 2013; Doudna, 2020; Fu Jinek 2013). While analysis such events have enabled the development Cas9 variants with greater discrimination against mismatches (Chen 2017; Kleinstiver 2016; Slaymaker 2016), underlying molecular mechanisms which rejects or accepts are poorly understood (Kim 2019; Liu and Gaudelli, 2021). Here, we used kinetic to guide cryo-EM structure...
Suppressor of IKK Epsilon (SIKE) is a protein in the virus‐ and TRL3‐triggered cascading signal pathway. SIKE has been shown to directly interact with alpha‐actinin, involved cytoskeletal rearrangement, coimmunoprecipitation vitro precipitation experiments. However, exact cellular processes affects are still unknown. To bridge this gap, we examined two that require migration phagocytosis, determine if functions these processes. Our model system parental cell line, HAP1, CRISPR/Cas9 knockout...
Signaling pathways of the innate immune system are essential conduits to cellular defenses against pathogen yet dysregulation or mutation often results in various autoimmune diseases, cancers, and other ailments. Obtaining a complete understanding native signal will facilitate identification complex defense mechanisms has potential yield molecular origins disease states. In Toll‐Like Receptor 3 (TLR3) pathway, Suppressor IKKepsilon (SIKE) undefined downstream function. Previous studies...
The first domain of modular polyketide synthases (PKSs) is most commonly a ketosynthase (KS)-like enzyme, KSQ, that primes synthesis. Unlike downstream, chain-extending KSs usually fuse α-carboxyacyl groups to growing chains, it performs an extension-decoupled decarboxylation these generate primer units. When Pik127, model triketide synthase constructed from modules the pikromycin synthase, was studied by cryogenic electron microscopy (cryo-EM), dimeric didomain comprised KSQ and neighboring...
Protein-protein interactions (PPIs) are a crucial part of intracellular communication and function. The "rules" for specificity and/or selection protein-protein interaction not completely understood, but protein modifications, such as phosphorylation, have been implicated in this process. Suppressor IKKepsilon (SIKE) is associated with multiple, distinct proteins including TANK-binding kinase 1 (TBK1), STRIPAK (striatin-interacting phosphatase kinase), cytoskeletal tubulin actinin. Although...