A5044192296- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Electrochemical Analysis and Applications
- Neuroscience and Neuropharmacology Research
- Photosynthetic Processes and Mechanisms
- Metabolism, Diabetes, and Cancer
- Nicotinic Acetylcholine Receptors Study
- Amino Acid Enzymes and Metabolism
- Neuroscience and Neural Engineering
- Plant Stress Responses and Tolerance
- Drug Transport and Resistance Mechanisms
- Lipid Membrane Structure and Behavior
- Glycosylation and Glycoproteins Research
- Lipid metabolism and biosynthesis
- Advanced Electron Microscopy Techniques and Applications
- Plant nutrient uptake and metabolism
- Cell death mechanisms and regulation
- Cholesterol and Lipid Metabolism
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Plant Molecular Biology Research
- Protein Structure and Dynamics
Center for Life Sciences
2015-2024
Tsinghua University
2015-2024
Princeton University
2005-2024
Shenzhen Bay Laboratory
2024
Child Trends
2021-2022
Beijing Advanced Sciences and Innovation Center
2016-2020
State Key Laboratory of Membrane Biology
2016-2019
University of Illinois Urbana-Champaign
2017
University of British Columbia
2007
TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets specific base pair using two hypervariable residues [known as variable diresidues (RVDs)] at positions 12 13. Here, we report the crystal structures an 11.5-repeat effector in both DNA-free DNA-bound states. helices connected short RVD-containing loop. The 11.5 repeats form...
Voltage-gated sodium (Nav) channels are responsible for the initiation and propagation of action potentials. They associated with a variety channelopathies targeted by multiple pharmaceutical drugs natural toxins. Here, we report cryogenic electron microscopy structure putative Nav channel from American cockroach (designated NavPaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) four repeats exhibit distinct conformations. entrance to asymmetric selectivity filter vestibule...
Voltage-gated sodium channel Nav1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of human Nav1.7-β1-β2 complex bound to two combinations pore blockers and gating modifier toxins (GMTs), tetrodotoxin with protoxin-II saxitoxin huwentoxin-IV, both determined at overall resolutions 3.2 angstroms. The are nearly identical except minor shifts voltage-sensing domain II (VSDII), whose S3-S4 linker accommodates GMTs in similar manner. One...
Structures of voltage-gated sodium channels In “excitable” cells, like neurons and muscle a difference in electrical potential is used to transmit signals across the cell membrane. This regulated by opening or closing ion For example, mutations human (Na v ) are associated with disorders such as chronic pain, epilepsy, cardiac arrhythmia. Pan et al. report high-resolution structure Na channel, Shen structures an insect channel bound toxins that cause pufferfish shellfish poisoning humans....
Abstract The interactions between phytohormones are crucial for plants to adapt complex environmental changes. One example is the ethylene-regulated local auxin biosynthesis in roots, which partly contributes ethylene-directed root development and gravitropism. Using a chemical biology approach, we identified small molecule, l-kynurenine (Kyn), effectively inhibited ethylene responses Arabidopsis thaliana tissues. Kyn application repressed nuclear accumulation of ETHYLENE INSENSITIVE3 (EIN3)...
The voltage-gated calcium channel Ca(v)1.1 is engaged in the excitation-contraction coupling of skeletal muscles. complex consists pore-forming subunit α1 and auxiliary subunits α2δ, β, γ. We report structure rabbit determined by single-particle cryo-electron microscopy. four homologous repeats are arranged clockwise extracellular view. γ subunit, whose resembles claudins, interacts with voltage-sensing domain repeat IV (VSD(IV)), whereas cytosolic β located adjacent to VSD(II) α1. α2 loops...
Gating a calcium channel The type 2 ryanodine receptor (RyR2) controls the release of ions from sarcoplasmic reticulum in cardiac cells—the initiating step muscle contraction. Mutations RyR2 are associated with diseases. Peng et al. used single-particle electron cryomicroscopy to determine structure porcine heart at 4.4-Å resolution closed and 4.2-Å open. structures reveal how interdomain motions result conformational change cytoplasmic region that is transduced by central domain cause open...
Animal toxins that modulate the activity of voltage-gated sodium (Nav) channels are broadly divided into two categories-pore blockers and gating modifiers. The pore tetrodotoxin (TTX) saxitoxin (STX) responsible for puffer fish shellfish poisoning in humans, respectively. Here, we present structures insect Nav channel NavPaS bound to a modifier toxin Dc1a at 2.8 angstrom-resolution presence TTX or STX 2.6-Å 3.2-Å resolution, inserts cleft between VSDII NavPaS, making key contacts with both...
Targeting sodium channels Voltage-gated (Na v ) have been implicated in cardiac and neurological disorders. There are many subtypes of these channels, making it challenging to develop specific therapeutics. A core α subunit is sufficient for voltage sensing ion conductance, but function modulated by β subunits natural toxins that can either act as pore blockers or gating modifiers (see the Perspective Chowdhury Chanda). Shen et al. present structures Na 1.7 complex with both β1 β2 animal...