Search results for "formation"
showing 10 items of 21020 documents
Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport
2017
Ion translocation across biological barriers is a fundamental requirement for life. In many cases, controlling this process-for example with neuroactive drugs-demands an understanding of rapid and reversible structural changes in membrane-embedded proteins, including ion channels and transporters. Classical approaches to electrophysiology and structural biology have provided valuable insights into several such proteins over macroscopic, often discontinuous scales of space and time. Integrating these observations into meaningful mechanistic models now relies increasingly on computational methods, particularly molecular dynamics simulations, while surfacing important challenges in data manage…
Insights into the inhibited form of the redox-sensitive SufE-like sulfur acceptor CsdE
2017
17 p.-8 fig.
Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers
2018
Influenza hemagglutinin (HA) is the canonical type I viral envelope glycoprotein and provides a template for the membrane-fusion mechanisms of numerous viruses. The current model of HA-mediated membrane fusion describes a static "spring-loaded" fusion domain (HA2) at neutral pH. Acidic pH triggers a singular irreversible conformational rearrangement in HA2 that fuses viral and cellular membranes. Here, using single-molecule Förster resonance energy transfer (smFRET)-imaging, we directly visualized pH-triggered conformational changes of HA trimers on the viral surface. Our analyses reveal reversible exchange between the pre-fusion and two intermediate conformations of HA2. Acidification of p…
The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition
2018
International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …
Evaluating the stability of pharmacophore features using molecular dynamics simulations.
2016
Abstract Molecular dynamics simulations of twelve protein—ligand systems were used to derive a single, structure based pharmacophore model for each system. These merged models combine the information from the initial experimental structure and from all snapshots saved during the simulation. We compared the merged pharmacophore models with the corresponding PDB pharmacophore models, i.e., the static models generated from an experimental structure in the usual manner. The frequency of individual features, of feature types and the occurrence of features not present in the static model derived from the experimental structure were analyzed. We observed both pharmacophore features not visible in …
Plasmin-Induced Activation of Human Platelets Is Modulated by Thrombospondin-1, Bona Fide Misfolded Proteins and Thiol Isomerases
2020
Inflammatory processes are triggered by the fibrinolytic enzyme plasmin. Tissue-type plasminogen activator, which cleaves plasminogen to plasmin, can be activated by the cross-&beta
Whole-genome sequencing for TB source investigations : principles of ethical precision public health
2021
[Background]: Whole-genome sequencing (WGS) of Mycobacterium tuberculosis allows rapid, accurate inferences about the sources, location and timing of transmission. However, in an era of heightened concern for personal privacy and science distrust, such inferences could result in unintended harm and undermine the public's trust.
Endogenous β-neurexins on axons and within synapses show regulated dynamic behavior
2021
Summary: Neurexins are key organizer molecules that regulate synaptic function and are implicated in autism and schizophrenia. β-neurexins interact with numerous cell adhesion and receptor molecules, but their neuronal localization remains elusive. Using single-molecule tracking and high-resolution microscopy to detect neurexin1β and neurexin3β in primary hippocampal neurons from knockin mice, we demonstrate that endogenous β-neurexins are present in fewer than half of excitatory and inhibitory synapses. Moreover, we observe a large extrasynaptic pool of β-neurexins on axons and show that axonal β-neurexins diffuse with higher surface mobility than those transiently confined within synapses…
Differential localization of voltage-gated potassium channels duringDrosophilametamorphosis
2020
Neuronal excitability is determined by the combination of different ion channels and their sub-neuronal localization. This study utilizes protein trap fly strains with endogenously tagged channels ...
Innovative Strategies to Develop Chemical Categories Using a Combination of Structural and Toxicological Properties.
2016
Interest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g., the European Union's Cosmetic Directive and REACH, demands the use of alternative methods. Frameworks, such as the Read-across Assessment Framework or the Adverse Outcome Pathway Knowledge Base, support the development of these methods. The aim of the project presented in this publication was to develop substance categories for a read-across with complex endpoints of toxicity based on existing databases. The basic conceptual approach was to combine str…