A5023623354- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Mass Spectrometry Techniques and Applications
- Electrochemical Analysis and Applications
- Advanced Electron Microscopy Techniques and Applications
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Force Microscopy Techniques and Applications
- Protein Structure and Dynamics
- Crystallography and molecular interactions
- Geophysical and Geoelectrical Methods
- Photoreceptor and optogenetics research
- Computational Drug Discovery Methods
- Spectroscopy and Quantum Chemical Studies
- Nanopore and Nanochannel Transport Studies
- Analytical Chemistry and Chromatography
- Analytical Chemistry and Sensors
- Bacterial Genetics and Biotechnology
- Geomagnetism and Paleomagnetism Studies
- Molecular Sensors and Ion Detection
- bioluminescence and chemiluminescence research
Stockholm University
2018-2024
Science for Life Laboratory
2018-2023
KTH Royal Institute of Technology
2023
Pentameric ligand-gated ion channels (pLGICs) are responsible for the rapid conversion of chemical to electrical signals. In addition canonical extracellular and transmembrane domains, some prokaryotic pLGICs contain an N-terminal domain (NTD) unclear structure function. one such case, calcium-sensitive channel DeCLIC, NTD appears accelerate gating; however, its evident flexibility has posed a challenge model building, role in calcium sensitivity is unclear. Here we report cryo-EM structures...
Ligand-gated ion channels are critical mediators of electrochemical signal transduction across evolution. The bacterial channel DeCLIC constitutes a provocative model system for structure, function, and dynamics in this family, including modulatory N-terminal domain (NTD). Previous closed structures support rationale its inhibition by calcium; however, properties open state remain unclear. Here we used cryogenic electron microscopy under acidic conditions to determine previously unreported...
Theories of general anesthesia have shifted in focus from bulk lipid effects to specific interactions with membrane proteins. Target receptors include several subtypes pentameric ligand-gated ion channels; however, structures physiologically relevant proteins this family yet define anesthetic binding at high resolution. Recent cocrystal the bacterial protein GLIC provide snapshots state-dependent sites for common surgical agent propofol (PFL), offering a detailed model system modulation....
Significance Ligand-gated ion channels are membrane proteins that cycle rapidly between open and closed forms, a process called gating. The structural basis of gating is foundational to receptor biophysics, cellular physiology, drug design; however, it remains unclear how experimental X-ray structures correspond solution behavior. Here, we test the structure model channel, GLIC, based on small-angle neutron scattering molecular simulations under conditions favor or states. We find...
Abstract Pentameric ligand-gated ion channels undergo subtle conformational cycling to control electrochemical signal transduction in many kingdoms of life. Several crystal structures have now been reported this family, but the functional relevance such models remains unclear. Here, we used small-angle neutron scattering (SANS) probe ambient solution-phase properties pH-gated bacterial channel GLIC under resting and activating conditions. Data collection was optimized by inline paused-flow...
Pentameric ligand-gated ion channels (pLGICs) perform electrochemical signal transduction in organisms ranging from bacteria to humans. Among the prokaryotic pLGICs, there is architectural diversity involving N-terminal domains (NTDs) not found eukaryotic relatives, exemplified by calcium-sensitive channel (DeCLIC) a Desulfofustis deltaproteobacterium, which has an NTD addition canonical pLGIC structure. Here, we have characterized structure and dynamics of DeCLIC through cryoelectron...
The resolution revolution has increasingly enabled single-particle cryogenic electron microscopy (cryo-EM) reconstructions of previously inaccessible systems, including membrane proteins-a category that constitutes a disproportionate share drug targets. We present protocol for using density-guided molecular dynamics simulations to automatically refine atomistic models into protein cryo-EM maps. Using adaptive force as implemented in the GROMACS package, we show how automated model refinement...
Pentameric ligand-gated ion channels (pLGICs) perform electrochemical signal transduction in organisms ranging from bacteria to humans [1].Among the prokaryotic pLGICs there is an architectural diversity involving N-terminal domains (NTDs) not found for eukaryotic relatives, exemplified by calcium-sensitive channel DeCLIC [2].Here [3], we characterized structure using cryogenic electron microscopy (cryo-EM), small-angle neutron scattering (SANS), and molecular dynamics (MD) simulations.In...
Abstract Pentameric ligand-gated ion channels (pLGICs) perform electrochemical signal transduction in organisms ranging from bacteria to humans. Among the prokaryotic pLGICs there is architectural diversity involving N-terminal domains (NTDs) not found eukaryotic relatives, exemplified by calcium-sensitive channel (DeCLIC) a Desulfofustis deltaproteobacterium, which has an NTD addition canonical pLGIC structure. Here we have characterized structure and dynamics of DeCLIC through...
I. ABSTRACT The resolution revolution has increasingly enabled single-particle cryogenic electron microscopy (cryo-EM) reconstructions of previously inaccessible systems, including membrane proteins – a category that constitutes disproportionate share drug targets. We present protocol for using density-guided molecular dynamics simulations to automatically refine atomistic models into membrane-protein cryo-EM maps. Using adaptive-force as implemented in the GROMACS package, we show how...