Gliadin, a protein present in wheat, rye, and barley, undergoes incomplete enzymatic degradation during digestion, producing an immunogenic 33-mer peptide, LQLQPF(PQPQLPY)3 PQPQPF. The special features of that provoke break its tolerance leading to gliadin sensitivity celiac disease remains elusive. Herein, it is reported peptide was not only able fold into polyproline II secondary structure but also depending on concentration resulted conformational transition self-assembly under aqueous...

The members of the Dicistroviridae family are non-enveloped positive-sense single-stranded RNA (+ssRNA) viruses pathogenic to beneficial arthropods as well insect pests medical importance. Triatoma virus (TrV), a member this family, infects several species triatomine insects (popularly named kissing bugs), which vectors for human trypanosomiasis, more commonly known Chagas disease. potential use dicistroviruses biological control agents has drawn considerable attention in past decade, and...

Cholinergic deficit is a characteristic factor of several pathologies, such as myasthenia gravis, some types congenital myasthenic syndromes, and Alzheimer's Disease. Two molecular targets for its treatment are acetylcholinesterase (AChE) nicotinic acetylcholine receptor (nAChR). In previous studies, we found that caffeine behaves partial nAChR agonist confirmed it inhibits AChE. Here, present new bifunctional derivatives consisting theophylline ring connected to amino groups by different...

In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in capsid small and non-enveloped icosahedral viruses. With purpose examine Triatoma Virus (TrV) as case study. This virus has stable under highly acidic conditions but disassembles releases genome alkaline environments. Our calculations range from subtle sub-atomic proton interchange to dismantling large-scale system representing several million atoms. results provide structure-based...

The proteolytic resistant 33-mer gliadin peptide is an immunodominant fragment in gluten and responsible for the celiac disease other gluten-related disorders. Meanwhile, primary structure of associated with adaptive immune response patients, structural transformation into protofilaments activates a primordial innate human macrophages. This means that accumulation, oligomerisation could be unknown first event triggers disease. Herein, we reveal early stepwise mechanism by combining multiple...

γ-aminobutyric acid-type A (GABAA) receptors mediate fast synaptic inhibition in the central nervous system of mammals. They are modulated via several sites by numerous compounds, which include GABA, benzodiazepines, ethanol, neurosteroids and anaesthetics among others. Due to their potential as targets novel drugs, a detailed knowledge structure–function relationships is needed. Here, we present model α1β2γ2 subtype GABAA receptor APO state complex with selected ligands, including agonists,...

Abstract Our research aimed to elucidate the mechanism by which aurintricarboxylic acid (ATA) inhibits plasma membrane Ca 2+ -ATPase (PMCA), a crucial enzyme responsible for calcium transport. Given pivotal role of PMCA in cellular homeostasis, understanding how it is inhibited ATA holds significant implications potentially regulating physiopathological processes this pump involved. experimental findings revealed that employs multiple modes action inhibit activity, are influenced ATP but...

The blood-sucking reduviid bug Triatoma infestans, one of the most important vector American human trypanosomiasis (Chagas disease) is infected by virus (TrV). TrV has been classified as a member Cripavirus genus (type cricket paralysis virus) in Dicistroviridae family. This work presents three-dimensional cryo-electron microscopy (cryo-EM) reconstruction capsid at about 25 Å resolution and its use template for phasing available crystallographic data molecular replacement method. main...

The structure of the endoglucanase A from Clostridium thermocellum CelA was re-solved by three-wavelength MAD. Experimental phases were obtained in resolution range 25-1.0 A. Various structure-solution approaches tested order to quantify contribution each wavelength. Two-wavelength MAD phasing sufficient obtain excellent experimental phases. SAD at remote wavelength also resulted interpretable maps. electron-density map quality: for parts structure, atom types and bond could be easily...

The X-ray structure of the tetragonal form apo acyl-CoA-binding protein (ACBP) from Harderian gland South American armadillo Chaetophractus villosus has been solved. ACBP is a carrier for activated long-chain fatty acids and associated with many aspects lipid metabolism. Its secondary highly similar to that corresponding bovine exhibits unique flattened α-helical bundle (up–down–down–up) motif reported animal, yeast insect ACBPs. Conformational differences are located in loops turns,...

The 33-mer gliadin peptide and its deamidated metabolite, DGP, are the immunodominant peptides responsible for adaptive immune response in celiac disease (CD). CD is a complex autoimmune chronic disorder triggered by gluten ingestion that affects small intestine ∼1% of global population. 33-mers polyproline II-rich (PPII) intrinsically disordered (IDPs), whose structures remain elusive. We sampled conformational ensembles both via molecular dynamics simulations employing two force fields...

Based on the analysis of mechanism ligand transfer to membranes employing in vitro methods, Fatty Acid Binding Protein (FABP) family has been divided two subgroups: collisional and diffusional FABPs. Although well characterized structural features responsible for difference between mechanisms remain uncertain. In this work, we have identified amino acids putatively interaction with both, diffusional, subgroups Moreover, show how specific changes FABPs' structure could change membranes. We...

Gluten related-disorders have a prevalence of 1-5 % worldwide triggered by the ingestion gluten proteins in wheat, rye, barley, and some oats. In wheat gluten, most studied protein is gliadin, whose immunodominant 33-mer amino acid fragment remains after digestive proteolysis accumulates gut mucosa. Here, we report formation thin-plate superstructures using intrinsic tyrosine (Tyr) steady-state fluorescence anisotropy cryo-TEM combination with water tension measurements. Furthermore, showed...

Triatoma virus (TrV) is a viral pathogen of the blood-sucking reduviid bug infestans, most important vector American human trypanosomiasis (Chagas' disease). TrV has been putatively classified as member Cripavirus genus (type cricket paralysis virus) in Dicistroviridae family. This work describes purification particles from infected T. infestans and their crystallization preliminary crystallographic analyses. Two different crystal forms, rhombohedral orthorhombic, were obtained at room...