A5017794289- Nanopore and Nanochannel Transport Studies
- Bacteriophages and microbial interactions
- Advanced biosensing and bioanalysis techniques
- Ion channel regulation and function
- RNA Interference and Gene Delivery
- Particle accelerators and beam dynamics
- Neuroscience and Neural Engineering
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Streptococcal Infections and Treatments
- Medical Imaging and Pathology Studies
- Lipid Membrane Structure and Behavior
- bioluminescence and chemiluminescence research
- Microtubule and mitosis dynamics
- Fuel Cells and Related Materials
- Photoreceptor and optogenetics research
- American Constitutional Law and Politics
- Microfluidic and Capillary Electrophoresis Applications
- Membrane-based Ion Separation Techniques
- Inorganic Fluorides and Related Compounds
- Lung Cancer Diagnosis and Treatment
- ATP Synthase and ATPases Research
- Infective Endocarditis Diagnosis and Management
- Bacterial Genetics and Biotechnology
Cornell University
2025
Washington University in St. Louis
2022-2024
University of Washington
2018-2024
Icahn School of Medicine at Mount Sinai
2023
Lehigh University
2014
Abstract Hyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking rhythmic electrical circuits human body. Unlike most voltage-gated channels, HCN related plant activate upon membrane hyperpolarization. Although functional studies have identified residues interface between voltage-sensing pore domain as crucial inverted electromechanical coupling, structural mechanisms this unusual voltage-dependence remain...
G protein-gated inwardly rectifying potassium (GIRK) channels mediate membrane hyperpolarization in response to protein-coupled receptor activation and are critical for regulating neuronal excitability. The phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) is essential a large family of ion channels, disruptions PIP2 interactions contribute some neurological diseases. Structural analyses have identified key residues PIP2-mediated gating the GIRK2 channel. Notably, Arginine-92 (R92),...
Inward rectifier Kir4.1 potassium channels are abundantly expressed in cells that important for electrolyte homeostasis. Dysregulation of underlies various neurological disorders. Here, through biochemical and structural studies full-length Kir4.1, we show dynein light chain 1 2 proteins, also as known LC8, co-purify with at stoichiometric levels. Direct interaction between LC8 is supported by vitro binding assays reiterated native proteins from mouse brain. Notably, identify a motif the...
Motor enzymes that process nucleic-acid substrates play vital roles in all aspects of genome replication, expression, and repair. The DNA RNA nucleobases are known to affect the kinetics these systems biologically meaningful ways. Recently, it was shown bases control translocation speed helicases on single-stranded DNA, however cause effects remains unclear. We use single-molecule picometer-resolution nanopore tweezers (SPRNT) measure along by helicase Hel308 from Thermococcus gammatolerans....
RNA polymerases (RNAPs) carry out the first step in central dogma of molecular biology by transcribing DNA into RNA. Despite their importance, much about how RNAPs work remains unclear, part because small (3.4 Angstrom) and fast (~40 ms/nt) steps during transcription were difficult to resolve. Here, we used high-resolution nanopore tweezers observe motion single Escherichia coli RNAP molecules as it transcribes ~1,000 times improved temporal resolution, resolving single-nucleotide...
The binding of bacteria to platelets is thought be a central event in the pathogenesis infective endocarditis. serine-rich repeat (SRR) glycoproteins viridans group streptococci have been shown mediate platelet vitro and contribute virulence animal models. However, it not known whether SRR adhesins can streptococcal under high fluidic shear stress conditions present on endocardial surface. We found that three (GspB, Hsa, SrpA) with differing structures sialoglycan specificities nevertheless...
We used single-molecule picometer-resolution nanopore tweezers (SPRNT) to resolve the millisecond single-nucleotide steps of superfamily 1 helicase PcrA as it translocates on, or unwinds, several kilobase-long DNA molecules. recorded more than two million enzyme under various assisting and opposing forces in diverse adenosine tri- diphosphate conditions comprehensively explore mechanochemistry motion. Forces applied SPRNT mimic physical barriers experiences vivo , such when encounters bound...
Abstract Mechanosensitive channels of small conductance, found in many living organisms, open under elevated membrane tension and thus play crucial roles biological response to mechanical stress. Amongst these channels, MscK is unique that its activation also requires external potassium ions. To better understand this dual gating mechanism by force ligand, we elucidate distinct structures along the cycle using cryo-electron microscopy. The heptameric channel comprises three layers: a...
Abstract The human Mitochondrial RNA Splicing 2 protein (MRS2) has been implicated in Mg 2+ transport across mitochondrial inner membranes, thus playing an important role homeostasis critical for integrity and function. However, the molecular mechanisms underlying its fundamental channel properties such as ion selectivity regulation remain unclear. Here, we present structural functional investigation of MRS2. Cryo-electron microscopy structures various ionic conditions reveal a pentameric...
Abstract Helicases are essential for nearly all nucleic acid processes across the tree of life, yet detailed understanding how they couple ATP hydrolysis to translocation and unwinding remains incomplete because their small (∼300 picometer), fast (∼1 ms) steps difficult resolve. Here, we use Nanopore Tweezers observe single Escherichia coli RecQ helicases as translocate on unwind DNA at ultrahigh spatiotemporal resolution. simultaneously resolve individual along conformational changes...
ABSTRACT Hyperpolarization and cyclic-nucleotide (HCN) activated ion channels play a critical role in generating self-propagating action potentials pacemaking rhythmic electrical circuits the human body. Unlike most voltage-gated channels, HCN activate upon membrane hyperpolarization, but structural mechanisms underlying this gating behavior remain unclear. Here, we present cryo-electron microscopy structures of HCN1 Closed, Intermediate, Open states. Our reveal that inward motion two...
Abstract We used single-molecule nanopore tweezers (SPRNT) to resolve the millisecond single-nucleotide steps of Superfamily 1 helicase PcrA as it translocates on, or unwinds, several kb-long DNA molecules. recorded over 2 million enzyme under various assisting and opposing forces in diverse ATP ADP conditions comprehensively explore mechanochemistry motion. Forces applied SPRNT mimic physical barriers experiences vivo , such when encounters bound proteins duplex DNA; we show how PcrA’s...