FoldScript: a web server for the efficient analysis of AI-generated 3D protein models.

Artificial intelligence (AI)-based 3D protein modelling software have revolutionized structural biology, often predicting protein structures with unprecedented confidence. However, to get the most out of AI, it is advisable to consider the information provided by a set of 'best' models with similar reliability scores, rather than just the top-ranked model, and to compare the results of different AI predictors. Furthermore, the 'highest scoring' solution is not always the 'best' one, especially in the case of oligomeric models where it may be crucial to introduce experimental knowledge into their selection.

Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization.

Human Immunodeficiency Virus (HIV) belongs to the Lentivirus genus, Retroviridae family, enveloped by a lipid bilayer within which the capsid protein encases the viral genome, reverse transcriptase, and integrase proteins, key components for viral replication. Viral capsid has been linked to key early and late stages of viral infection, including nuclear entry, promoting reverse transcription and assembly of new viral particles within target TCD4+ lymphocytes. Effective treatments for HIV involve multi drug therapy, which can reduce the patient's viral load to undetectable values, thus avoiding the appearance of Acquired Immunodeficiency Syndrome (AIDS).

Impact of Gd doping on structural and magnetic characteristics of SrFeOperovskite nanomaterial.

The SrFeOnanoparticles doped with 5% and 10% Gd were synthesized using the solution combustion method. The phase formation of the synthesized nanoparticles was confirmed by powder x-ray diffraction analysis. Field emission scanning electron microscope and HRTEM were employed to examine the morphology of the samples, revealing well-ordered, agglomerated nanoparticles.

Unveiling a Shield of Hope: A Novel Multiepitope-Based Immunogen for Cross-Serotype Cellular Defense against Dengue Virus.

Dengue virus (DENV) infection continues to be a public health challenge, lacking a specific cure. Vaccination remains the primary strategy against dengue; however, existing live-attenuated vaccines display variable efficacy across four serotypes, influenced by host serostatus and age, and predominantly inducing humoral responses. To address this limitation, this study investigates a multiepitope-based immunogen designed to induce robust cellular immunity across all DENV serotypes.

"It's Only a Model": When Protein Structure Predictions Need Experimental Validation, the Case of the HTLV-1 Tax Protein.

Human T-cell Leukemia Virus type 1 (HTLV-1) is a human retrovirus responsible for leukaemia in 5 to 10% of infected individuals. Among the viral proteins, Tax has been described as directly involved in virus-induced leukemogenesis. Tax is therefore an interesting therapeutic target.

Purine containing carbonucleoside phosphonate analogues as novel chemotype for Plasmodium falciparum Inhibition.

The nucleotidase ISN1 is a potential therapeutic target of the purine salvage pathway of the malaria parasite Plasmodium falciparum. We identified PfISN1 ligands by in silico screening of a small library of nucleos(t)ide analogues and by thermal shift assays. Starting from a racemic cyclopentyl carbocyclic phosphonate scaffold, we explored the diversity on the nucleobase moiety and also proposed a convenient synthetic pathway to access the pure enantiomers of our initial hit (compound (±)-2).

Specific Xray diffraction patterns of membrane proteins caused by secondary structure collinearity.

Diffraction anisotropy is a phenomenon that impacts more specifically membrane proteins, compared to soluble ones, but the reasons for this discrepancy remained unclear. Often, it is referred to a difference in resolution limits between highest and lowest diffraction limits as a signature for anisotropy. We show in this article that there is no single correlation between anisotropy and difference in resolution limits, with notably a substantial number of structures displaying various anisotropy with no difference in resolution limits.

Identification of 2-(4-N,N-Dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo.

The capsid (CA) subunit of the HIV-1 Gag polyprotein is involved in several steps of the viral cycle, from the assembly of new viral particles to the protection of the viral genome until it enters into the nucleus of newly infected cells. As such, it represents an interesting therapeutic target to tackle HIV infection. In this study, we screened hundreds of compounds with a low cost of synthesis for their ability to interfere with Gag assembly in vitro.

First Apatite (U-Th)/He and apatite fission-track thermochronology dataset from the Abancay Deflection (Eastern Cordillera, Southern Peru).

According to their respective temperature sensitivities, Apatite (U-Th)/He (AHe) and apatite fission-track (AFT) thermochronology records the thermal evolution of the upper crust (<5 km) and is a key for distinguishing between different exhumation mechanisms through time-evolving rock uplift, and landscape evolution. We applied these methods to extract the thermal evolution of the upper crust in the Abancay Deflection at the northern edge of the Altiplano (southern Peru). We present 120 single-crystal AHe ages (from 31 samples) and 27 AFT central ages obtained from magmatic bodies across the study area.

CryoEM reconstructions of membrane proteins solved in several amphipathic solvents, nanodisc, amphipol and detergents, yield amphipathic belts of similar sizes corresponding to a common ordered solvent layer.

To maintain membrane proteins soluble in aqueous solution, amphipathic compounds are used to shield the hydrophobic patch of their membrane insertion, which forms a belt around the protein. This amphipathic belt is seldom looked at due to the difficulty to visualize it. Cryo-EM is now offering this possibility, where belts are visible in 3D reconstructions.

Exploring molecular determinants of polysaccharide lyase family 6-1 enzyme activity.

The polysaccharide lyase family 6 (PL6) represents one of the 41 polysaccharide lyase families classified in the CAZy database with the vast majority of its members being alginate lyases grouped into three subfamilies, PL6_1-3. To decipher the mode of recognition and action of the enzymes belonging to subfamily PL6_1, we solved the crystal structures of Pedsa0632, Patl3640, Pedsa3628 and Pedsa3807, which all show different substrate specificities and mode of action (endo-/exolyase). Thorough exploration of the structures of Pedsa0632 and Patl3640 in complex with their substrates as well as docking experiments confirms that the conserved residues in subsites -1 to +3 of the catalytic site form a common platform that can accommodate various types of alginate in a very similar manner but with a series of original adaptations bringing them their specificities of action.

Identification of a Potential Inhibitor of the FIV p24 Capsid Protein and Characterization of Its Binding Site.

Feline immunodeficiency virus (FIV) is a veterinary infective agent for which there is currently no efficient drug available. Drugs targeting the lentivirus capsid are currently under development for the treatment of human immunodeficiency virus 1 (HIV-1). Here we describe a lead compound that interacts with the FIV capsid.

Structure-function analysis of pectate lyase Pel3 reveals essential facets of protein recognition by the bacterial type 2 secretion system.

The type II secretion system (T2SS) transports fully folded proteins of various functions and structures through the outer membrane of Gram-negative bacteria. The molecular mechanisms of substrate recruitment by T2SS remain elusive but a prevailing view is that the secretion determinants could be of a structural nature. The phytopathogenic γ-proteobacteria, Pectobacterium carotovorum and Dickeya dadantii, secrete similar sets of homologous plant cell wall degrading enzymes, mainly pectinases, by similar T2SSs, called Out.

Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity.

Trematode infections such as schistosomiasis and fascioliasis cause significant morbidity in an estimated 250 million people worldwide and the associated agricultural losses are estimated at more than US$ 6 billion per year. Current chemotherapy is limited. Triosephosphate isomerase (TIM), an enzyme of the glycolytic pathway, has emerged as a useful drug target in many parasites, including Fasciola hepatica TIM (FhTIM).

Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase.

The integration of the retroviral genome into the chromatin of the infected cell is catalysed by the integrase (IN)•viral DNA complex (intasome). This process requires functional association between the integration complex and the nucleosomes. Direct intasome/histone contacts have been reported to modulate the interaction between the integration complex and the target DNA (tDNA).

computation of the PDB to audit diffraction anisotropy of soluble and membrane proteins.

This data article makes available the informed computation of the whole Protein Data Bank (PDB) to investigate diffraction anisotropy on a large scale and to perform statistics. This data has been investigated in detail in "X-ray diffraction reveals the intrinsic difference in the physical properties of membrane and soluble proteins" [1]. Diffraction anisotropy is traditionally associated with absence of contacts in-between macromolecules within the crystals in a given direction of space.

Looking for Novel Capsid Protein Multimerization Inhibitors of Feline Immunodeficiency Virus.

Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses. It causes acquired immunodeficiency syndrome (AIDS) in worldwide domestic and non-domestic cats and is a cause of an important veterinary issue. The genome organization of FIV and the clinical characteristics of the disease caused by FIV are similar to human immunodeficiency virus (HIV).

Identification and visualization of protein binding regions with the ArDock server.

ArDock (ardock.ibcp.fr) is a structural bioinformatics web server for the prediction and the visualization of potential interaction regions at protein surfaces.

X-ray diffraction reveals the intrinsic difference in the physical properties of membrane and soluble proteins.

Membrane proteins are distinguished from soluble proteins by their insertion into biological membranes. This insertion is achieved via a noticeable arrangement of hydrophobic amino acids that are exposed at the surface of the protein, and renders the interaction with the aliphatic tails of lipids more energetically favorable. This important difference between these two categories of proteins is the source of the need for a specific handling of membrane proteins, which transpired in the creation of new tools for their recombinant expression, purification and even crystallization.

Modulation of the functional association between the HIV-1 intasome and the nucleosome by histone amino-terminal tails.

Background: Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein-protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process.

Substrate recognition by the bacterial type II secretion system: more than a simple interaction.

Type II secretion system (T2SS) is a multiprotein trans-envelope complex that translocates fully folded proteins through the outer membrane of Gram-negative bacteria. Although T2SS is extensively studied in several bacteria pathogenic for humans, animals and plants, the molecular basis for exoprotein recruitment by this secretion machine as well as the underlying targeting motifs remain unknown. To address this question, we used bacterial two-hybrid, surface plasmon resonance, in vivo site-specific photo-cross-linking approaches and functional analyses.

Deciphering key features in protein structures with the new ENDscript server.

ENDscript 2 is a friendly Web server for extracting and rendering a comprehensive analysis of primary to quaternary protein structure information in an automated way. This major upgrade has been fully re-engineered to enhance speed, accuracy and usability with interactive 3D visualization. It takes advantage of the new version 3 of ESPript, our well-known sequence alignment renderer, improved to handle a large number of data with reduced computation time.

Dynamic interplay between the periplasmic and transmembrane domains of GspL and GspM in the type II secretion system.

The type II secretion system (T2SS) is a multiprotein nanomachine that transports folded proteins across the outer membrane of gram-negative bacteria. The molecular mechanisms that govern the secretion process remain poorly understood. The inner membrane components GspC, GspL and GspM possess a single transmembrane segment (TMS) and a large periplasmic region and they are thought to form a platform of unknown function.