Structural Analysis of the GSTome.

Glutathione transferase (GST) is a superfamily of ubiquitous enzymes, multigenic in numerous organisms and which generally present homodimeric structures. GSTs are involved in numerous biological functions such as chemical detoxification as well as chemoperception in mammals and insects. GSTs catalyze the conjugation of their cofactor, reduced glutathione (GSH), to xenobiotic electrophilic centers.

Significant influence of four highly conserved amino-acids in lipochaperon-active sHsps on the structure and functions of the Lo18 protein.

To cope with environmental stresses, bacteria have developed different strategies, including the production of small heat shock proteins (sHSP). All sHSPs are described for their role as molecular chaperones. Some of them, like the Lo18 protein synthesized by Oenococcus oeni, also have the particularity of acting as a lipochaperon to maintain membrane fluidity in its optimal state following cellular stresses.

Wild-Type -Synuclein and Variants Occur in Different Disordered Dimers and Pre-Fibrillar Conformations in Early Stage of Aggregation.

-Synuclein is a 140 amino-acid intrinsically disordered protein mainly found in the brain. Toxic -synuclein aggregates are the molecular hallmarks of Parkinson's disease. studies showed that -synuclein aggregates in oligomeric structures of several 10th of monomers and into cylindrical structures (fibrils), comprising hundred to thousands of proteins, with polymorphic cross--sheet conformations.

Missense Mutations Modify the Conformational Ensemble of the -Synuclein Monomer Which Exhibits a Two-Phase Characteristic.

-Synuclein is an intrinsically disordered protein occurring in different conformations and prone to aggregate in -sheet structures, which are the hallmark of the Parkinson disease. Missense mutations are associated with familial forms of this neuropathy. How these single amino-acid substitutions modify the conformations of wild-type -synuclein is unclear.

Nanopore sensing of single-biomolecules: a new procedure to identify protein sequence motifs from molecular dynamics.

Solid-state nanopores have emerged as one of the most versatile tools for single-biomolecule detection and characterization. Nanopore sensing is based on the measurement of variations in ionic current as charged biomolecules immersed in an electrolyte translocate through nanometer-sized channels, in response to an external voltage applied across the membrane. The passage of a biomolecule through a pore yields information about its structure and chemical properties, as demonstrated experimentally with sub-microsecond temporal resolution.

Curvature and Torsion of Protein Main Chain as Local Order Parameters of Protein Unfolding.

Thermal protein unfolding resembles a global (two-state) phase transition. At the local scale, protein unfolding is, however, heterogeneous and probe dependent. Here, we consider local order parameters defined by the local curvature and torsion of the protein main chain.

Molecular Dynamics Investigation of Polylysine Peptide Translocation through MoS Nanopores.

Solid-state nanopores (SSN) made of two-dimensional materials such as molybdenum disulfide (MoS) have emerged as candidate devices for biomolecules sequencing. SSN sequencing is based on measuring the variations in ionic conductance as charged biomolecules translocate through nanometer-sized channels, in response to an external voltage applied across the membrane. Although several experiments on DNA translocation through SSNs have been performed in the past decade, translocation of proteins has been less studied, partly due to small protein size and detection limits.

Data on the expression of and in Drosophila chemosensory organs after isothiocyanate exposure.

The data presented in this article are related to the research article entitled "Characterization of a Drosophila glutathione transferase involved in isothiocyanate detoxification." (Gonzalez et al., 2018) [1].

Characterization of a Drosophila glutathione transferase involved in isothiocyanate detoxification.

Glutathione transferases (GSTs) are ubiquitous key enzymes that catalyse the conjugation of glutathione to xenobiotic compounds in the detoxification process. GSTs have been proposed to play a dual role in the signal termination of insect chemodetection by modifying odorant and tasting molecules and by protecting the chemosensory system. Among the 40 GSTs identified in Drosophila melanogaster, the Delta and Epsilon groups are insect-specific.

From a Highly Disordered to a Metastable State: Uncovering Insights of α-Synuclein.

α-Synuclein (αS) is a major constituent of Lewy bodies, the insoluble aggregates that are the hallmark of one of the most prevalent neurodegenerative disorders, Parkinson's disease (PD). The vast majority of experiments in vitro and in vivo provide extensive evidence that a disordered monomeric form is the predominant state of αS in water solution, and it undergoes a large-scale disorder-to-helix transition upon binding to vesicles of different types. Recently, another form, tetrameric, of αS with a stable helical structure was identified experimentally.

Statistical Model To Decipher Protein Folding/Unfolding at a Local Scale.

Protein folding/unfolding can be analyzed experimentally at a local scale by monitoring the physical properties of local probes as a function of the temperature, for example, the distance between fluorophores or the values of chemical shifts of backbone atoms. Here, the analytical Lifson-Roig model for the helix-coil transition is modified to analyze local thermal unfolding of the fast-folder W protein of bacteriophage lambda (gpW) simulated by all-atom molecular dynamics (MD) simulations in explicit solvent at 15 different temperatures. The protein structure is described by the coarse-grained dihedral angles (γ) and bond angles (θ) built between successive C-C virtual bonds.

Serum Gp96 is a chaperone of complement-C3 during graft-versus-host disease.

Better identification of severe acute graft-versus-host disease (GvHD) may improve the outcome of this life-threatening complication of allogeneic hematopoietic stem cell transplantation. GvHD induces tissue damage and the release of damage-associated molecular pattern (DAMP) molecules. Here, we analyzed GvHD patients ( = 39) to show that serum heat shock protein glycoprotein 96 (Gp96) could be such a DAMP molecule.

Fingerprints of Conformational States of Human Hsp70 at Sub-THz Frequencies.

Large multidomain proteins occur in different conformational states to function. Detection and monitoring of these different structural states are of crucial interest for understanding the mechanics of proteins. Using computational methods, we show that different protein conformational states of the two-domain 70 kDa human Heat-shock protein (hHsp70), with similar vibrational density of states, lead to remarkably different far-IR spectra at acoustical frequencies (ν < 300 GHz).

Theoretical Insights into Sub-Terahertz Acoustic Vibrations of Proteins Measured in Single-Molecule Experiments.

Proteins are an important class of nanobioparticles with acoustical modes in the sub-THz frequency range. There is considerable interest to measure and establish the role of these acoustical vibrations for biological function. So far, the technique providing the most detailed information about the acoustical modes of proteins is the very recent Extraordinary Acoustic Raman (EAR) spectroscopy.

Reducing the Use of Pesticides with Site-Specific Application: The Chemical Control of Rhizoctonia solani as a Case of Study for the Management of Soil-Borne Diseases.

Reducing our reliance on pesticides is an essential step towards the sustainability of agricultural production. One approach involves the rational use of pesticides combined with innovative crop management. Most control strategies currently focus on the temporal aspect of epidemics, e.

Intrinsic Localized Modes in Proteins.

Protein dynamics is essential for proteins to function. Here we predicted the existence of rare, large nonlinear excitations, termed intrinsic localized modes (ILMs), of the main chain of proteins based on all-atom molecular dynamics simulations of two fast-folder proteins and of a rigid α/β protein at 300 K and at 380 K in solution. These nonlinear excitations arise from the anharmonicity of the protein dynamics.

Effect of Washes and Centrifugation on the Efficacy of Lipofilling With or Without Local Anesthetic.

Background: Among the different parameters that influence fat graft survival and lipofilling success, the use of local anesthetic and the way to process the fat before injection have often been pointed out. Likewise, we evaluated different techniques for processing adipose tissue before its injection and analyzed the quality of the grafts.

Methods: Adipose tissue from the same patient was gently harvested from one side of the abdomen after infiltration of a tumescent solution without lidocaine and from the other side of the abdomen using a tumescent solution containing lidocaine 2%.

New Insights into Protein (Un)Folding Dynamics.

A fundamental open problem in biophysics is how the folded structure of the main chain (MC) of a protein is determined by the physics of the interactions between the side chains (SCs). All-atom molecular dynamics simulations of a model protein (Trp-cage) revealed that strong correlations between the motions of the SCs and the MC occur transiently at 380 K in unfolded segments of the protein and during the simulations of the whole amino-acid sequence at 450 K. The high correlation between the SC and MC fluctuations is a fundamental property of the unfolded state and is also relevant to unstructured proteins as intrinsically disordered proteins (IDPs), for which new reaction coordinates are introduced.

Interplay between parasitism and host ontogenic resistance in the epidemiology of the soil-borne plant pathogen Rhizoctonia solani.

Spread of soil-borne fungal plant pathogens is mainly driven by the amount of resources the pathogen is able to capture and exploit should it behave either as a saprotroph or a parasite. Despite their importance in understanding the fungal spread in agricultural ecosystems, experimental data related to exploitation of infected host plants by the pathogen remain scarce. Using Rhizoctonia solani / Raphanus sativus as a model pathosystem, we have obtained evidence on the link between ontogenic resistance of a tuberizing host and (i) its susceptibility to the pathogen and (ii) after infection, the ability of the fungus to spread in soil.

Patients with colorectal tumors with microsatellite instability and large deletions in HSP110 T17 have improved response to 5-fluorouracil–based chemotherapy.

Background & Aims: Patients with colorectal tumors with microsatellite instability (MSI) have better prognoses than patients with tumors without MSI, but have a poor response to 5-fluorouracil–based chemotherapy. A dominant-negative form of heat shock protein (HSP)110 (HSP110DE9) expressed by cancer cells with MSI, via exon skipping caused by somatic deletions in the T(17) intron repeat, sensitizes the cells to 5-fluorouracil and oxaliplatin.We investigated whether HSP110 T(17) could be used to identify patients with colorectal cancer who would benefit from adjuvant chemotherapy with 5-fluorouracil and oxaliplatin.

Decipher the mechanisms of protein conformational changes induced by nucleotide binding through free-energy landscape analysis: ATP binding to Hsp70.

ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD) simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL) of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD) of Hsp70 propagates a signal to its substrate-binding domain (SBD).

Effect of centrifugation and washing on adipose graft viability: a new method to improve graft efficiency.

Background: Adipose tissue grafting is a promising method in the field of surgical filling. We studied the effect of centrifugation on fat grafts, and we propose an optimised protocol for the improvement of adipose tissue viability.

Methods: Adipose tissue was subjected to different centrifugations, and the volumes of interstitial liquid and oil released were measured to choose the optimal condition.

New insights into lidocaine and adrenaline effects on human adipose stem cells.

Background: Adipose stem cells have gained great interest in plastic and reconstructive surgery with their ability to improve engraftment after fat transfer for soft tissue filling. It is therefore essential to know the effect of the drugs commonly used during the lipoaspiration procedure, such as lidocaine and adrenaline. Indeed, these drugs are infiltrated at the fat donor site for local anesthesia and for reduction of bleeding.

Conformational dynamics of full-length inducible human Hsp70 derived from microsecond molecular dynamics simulations in explicit solvent.

Human 70 kDa heat shock protein (hHsp70) is an ATP-dependent chaperone and is currently an important target for developing new drugs in cancer therapy. Knowledge of the conformations of hHsp70 is central to understand the interactions between its nucleotide-binding domain (NBD) and substrate-binding domain (SBD) and is a prerequisite to design inhibitors. The conformations of ADP-bound (or nucleotide-free) hHsp70 and ATP-bound hHsp70 was investigated by using unbiased all-atom molecular dynamics (MD) simulations of homology models of hHsp70 in explicit solvent on a timescale of .

Anomalous diffusion and dynamical correlation between the side chains and the main chain of proteins in their native state.

Structural fluctuations of a protein are essential for a protein to function and fold. By using molecular dynamics (MD) simulations of the model α/β protein VA3 in its native state, the coupling between the main-chain (MC) motions [represented by coarse-grained dihedral angles (CGDAs) γ(n) based on four successive C(α) atoms (n - 1, n, n + 1, n + 2) along the amino acid sequence] and its side-chain (SC) motions [represented by CGDAs δ(n) formed by the virtual bond joining two consecutive C(α) atoms (n, n + 1) and the bonds joining these C(α) atoms to their respective C(β) atoms] was analyzed. The motions of SCs (δ(n)) and MC (γ(n)) over time occur on similar free-energy profiles and were found to be subdiffusive.