A5069697717- RNA and protein synthesis mechanisms
- Ion channel regulation and function
- Blood Coagulation and Thrombosis Mechanisms
- Corporate Governance and Management
- RNA modifications and cancer
- Lipid Membrane Structure and Behavior
- RNA Research and Splicing
- Erythrocyte Function and Pathophysiology
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
- Sports Science and Education
- Animal Disease Management and Epidemiology
- Heat shock proteins research
- Photoreceptor and optogenetics research
- Prion Diseases and Protein Misfolding
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Connexins and lens biology
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Advanced Electron Microscopy Techniques and Applications
- Nicotinic Acetylcholine Receptors Study
- Bacterial Genetics and Biotechnology
- Alzheimer's disease research and treatments
- HIV/AIDS drug development and treatment
Washington University in St. Louis
2012-2024
Bayer (United States)
2024
Stanford University
2023-2024
Washington Center
2021
University Hospital Ulm
2011
University of Sussex
1993-2003
École Normale Supérieure de Lyon
2000
Inserm
2000
Laboratoire d'Electrochimie Moléculaire
2000
Laboratoire de Biochimie
1995
How amyloid can be a substrate of memory Formation memories requires changes in the molecular composition synapse. these occur and what maintains this altered synaptic so that persist are unknown. Hervas et al. report structure translation regulator called Orb2 isolated from brains adult fruit flies is important for maintenance recall memory. forms an its activity repressor to activator. The core composed polar hydrophilic residues, as opposed hydrophobic ones found nonfunctional or...
Lipid nanodiscs have become a standard tool for studying membrane proteins, including using single particle cryo-electron microscopy (cryo-EM). We find that reconstituting the pentameric ligand-gated ion channel (pLGIC), Erwinia (ELIC), in different produces distinct structures by cryo-EM. The effect of nanodisc on ELIC structure extends to extracellular domain and agonist binding site. Additionally, molecular dynamic simulations indicate size impact scaffold directly interacts with ELIC....
Abstract The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation alpha-synuclein (Asyn) fibrils in bodies neurites. Here we develop validate a method to amplify Asyn extracted from LBD postmortem tissue samples use solid state nuclear magnetic resonance (SSNMR) studies determine atomic resolution structure. Amplified comprise mixture single protofilament two with very low twist. fold highly similar determined by recent cryo-electron microscopy study...
Abstract The intrinsic and extrinsic pathways of the coagulation cascade converge to a common step where prothrombinase complex, comprising enzyme factor Xa (fXa), cofactor fVa, Ca2+ phospholipids, activates zymogen prothrombin protease thrombin. reaction entails cleavage at 2 sites, R271 R320, generating intermediates prethrombin meizothrombin, respectively. molecular basis these interactions that are central hemostasis remains elusive. We solved cryogenic electron microscopy (cryo-EM)...
The cap-binding eukaryotic initiation factor, eIF4E, is a key target for the regulation of translation in mammalian cells and widely thought to be present at very low molar concentrations. Here we observations with reticulocyte lysate that challenge this view. When ribosomes are harvested by centrifugation, most (75%) eIF4E remains postribosomal supernatant (PRS). In reconstituted system find ribosome-associated alone can sustain much overall activity, suggesting factor PRS functionally...
Abstract Mechanosensitive ion channels transduce physical force into electrochemical signaling that underlies an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis. The mechanosensitive small conductance (MscS) constitute a remarkably diverse superfamily critical for management osmotic pressure. Here, we present cryo-electron microscopy structures MscS homolog from Arabidopsis thaliana , MSL1, presumably in both the...
Cryo-EM reveals structural insights into a new class of chloride channels that underlies acid-sensitive anion currents.
Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia channel), positively modulated by anionic phospholipid, phosphatidylglycerol, from outer leaflet membrane. To explore phosphatidylglycerol modulation, we determine a structure in an open-channel conformation. shows bound site, structural changes...
Coagulation factor V (fV) is the inactive precursor of fVa, an essential component prothrombinase complex required for rapid activation prothrombin in penultimate step coagulation cascade. In addition, fV regulates tissue pathway inhibitor α (TFPIα) and protein C pathways that inhibit response. A recent cryogenic electron microscopy (cryo-EM) structure has revealed architecture its A1-A2-B-A3-C1-C2 assembly but left mechanism keeps state unresolved due to intrinsic disorder B domain. splice...
Abstract The pannexin 2 channel (PANX2) participates in multiple physiological processes including skin homeostasis, neuronal development, and ischemia-induced brain injury. However, the molecular basis of PANX2 function remains largely unknown. Here, we present a cryo-electron microscopy structure human PANX2, which reveals pore properties contrasting with those intensely studied paralog PANX1. extracellular selectivity filter, defined by ring basic residues, more closely resembles that...
Abstract Homologous recombination (HR) is an essential double-stranded DNA break repair pathway. In HR, Rad52 facilitates the formation of Rad51 nucleoprotein filaments on RPA-coated ssDNA. Here, we decipher how functions using single-particle cryo-electron microscopy and biophysical approaches. We report that a homodecameric ring each subunit possesses ordered N-terminal disordered C-terminal half. An intrinsic structural asymmetry observed where few halves interact with ring. describe two...
Infection of cells with the foot-and-mouth-disease virus, a member picornavirus family, results in shut-off host protein synthesis. A major contributory mechanism is proteolytic destruction γ subunit complex elF-4, which functions translation to promote binding 43S ribosomal preinitiation 5′ end cellular mRNA molecules bearing terminal cap structure. Picornavirus RNA molecules, are uncapped, use distinct for translational initiation, can operate absence, or at low levels, elF-4. The...
Mature porcine peripheral blood mononuclear cells (PPBMCs) exist in a resting state both vivo and when maintained culture, with low translation rates consistent their non‐proliferative state. When cultured the presence of appropriate mitogen, there is 2–4‐fold increase rate protein synthesis per ribosome within 4 h stimulation [Kay, J. E., Ahern, T. Atkins, M. (1971) Biochim. Biophys. Acta 247 , 322–334]. Studies on extracts prepared from unstimulated have suggested lesions initiation factor...
Phytochromes (Phys) are a divergent cohort of bili-proteins that detect light through reversible interconversion between dark-adapted Pr and photoactivated Pfr states. While our understandings downstream events emerging, it remains unclear how Phys translate into an interpretable conformational signal. Here, we present models both states for dimeric Phy with histidine kinase (HK) activity from the proteobacterium Pseudomonas syringae, which were built high-resolution cryo-EM maps (2.8-3.4-Å)...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has necessitated the rapid development of antibody-based therapies and vaccines as countermeasures. Here, we use cryoelectron microscopy (cryo-EM) to characterize two protective anti-SARS-CoV-2 murine monoclonal antibodies (mAbs) in complex with spike protein, revealing similarities between epitopes targeted by human B cells. more neutralizing mAb, 2B04, binds receptor-binding motif (RBM) domain (RBD) competes...
The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation alpha-synuclein (Asyn) fibrils in bodies neurites. We developed validated a novel method to amplify Asyn extracted from LBD postmortem tissue samples used solid state nuclear magnetic resonance (SSNMR) studies determine atomic resolution structure. Amplified comprise two protofilaments with pseudo-2
Homologous recombination (HR) is a pathway for the accurate repair of double-stranded DNA breaks. These breaks are resected to yield single-stranded (ssDNA) that coated by Replication Protein A (RPA).
Stem–loop II of U1 snRNA and IV U2 typically have 10 or 11 nucleotides in their loops. The fluorescent nucleobase 2-aminopurine was used as a substitute for the adenines each loop to probe local global structures dynamics these unusually long Using steady-state time-resolved fluorescence, we find that, while bases loops are stacked, they able undergo significant motion on picosecond/nanosecond timescale. In addition, conformational change at low temperatures that occurs microsecond...