Press-room / Digest
New Type of Interaction of Snake Three-Finger α-Neurotoxins with Nicotinic Acetylcholine Receptors
In a new work, the researches of the Laboratory of Bioengineering of Neuroreceptors and Neuromodulators, the Laboratory of Structural Biology of Ion Channels, the Group for Analysis of the Structure of Membrane Proteins in Silico, and Laboratory of Biomolecular Modeling of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, together with the researches of the National Research Center «Kurchatov Institute», Institute of Biomedical Chemistry, and Lomonosov Moscow State University using α-bungarotoxin (classical three-finger α-neurotoxin with high affinity to α7-nAChR), we showed applicability of cryo-EM to study interactions of α7-nAChR extracellular ligand-binding domain (α7-ECD) with its ligands, despite the proximity of the size of the complex to the lower limit of the sizes of biomolecules available for study by this method of structural biology. The study is published in the Communications Biology. Learn more
Identification of HLA-B*27-bound peptides recognized by TCRs associated with ankylosing spondylitis
A team of scientists from the Laboratory of comparative and functional genomics of IBCh RAS in collaboration with researchers from Universities of Stanford and Oxford, as wells as Washington University of St. Louis described structure and peptide motif recognized by T cell receptors (TCRs) associated with ankylosing spondylitis (AS). Structural analysis of TCRpMHC complexes allowed to identify shared binding motif present in both self-antigens and microbial antigens that engages AS-related TCRs. These findings support the hypothesis that cross-reactivity between microbial and self-antigens can be considered as a trigger event for pathogenesis of ankylosing spondylitis. The results of the study have been recently published in Nature. Learn more
Relationship between phenolic compounds and antioxidant activity in berries and leaves of raspberry genotypes and their genotyping using SSR markers
Researchers from the Forest Biotechnology Group of the FIBCh together with colleagues from other institutes studied the content of total phenols, flavonoids and anthocyanins, their relationship with the antioxidant activity of berries and leaves of various raspberry cultivars of Russian and foreign origin, as well as new breeding lines. An optimal method for the analysis of antioxidant activity of raspberry was determined, breeding lines superior to standard cultivars were identified, and phenological phases for the maximum bioactive value of raspberry plants were established. In addition, for the first time, the relationship between the chemical diversity of plant cultivars and genetic markers specific for a particular metabolic pathway was studied. The strong correlation between biochemical and genetic data makes it possible to use these markers in the selection for improving nutritional properties, as well as to study the mechanisms of flower and fruit color formation. The study published in Antioxidants. Learn more
A Single Fluorescent Protein-Based Indicator with a Time-Resolved Fluorescence Readout for Precise pH Measurements in the Alkaline Range
The real-time monitoring of the intracellular pH in live cells with high precision represents an important methodological challenge. Most of the genetically encoded fluorescent indicators are hindered by the inability to determine an absolute pH value and/or a narrow dynamic range of the signal. The team of scientists from the Laboratory of genetically encoded molecular tools IBCh RAS studied the pH sensitivity of a green-fluorescence-protein (GFP)-based emitter (EGFP-Y145L/S205V) with the alkaline-shifted chromophore’s pKa and demonstrate that, in the pH range of 7.5–9.0, its fluorescence lifetime changes by a factor of ~3.5 in a quasi-linear manner in mammalian cells. Considering the relatively strong lifetime response in a narrow pH range, authors proposed the mitochondria, which are known to have a weakly alkaline milieu, as a target for live-cell pH measurements. Using FLIM they succeeded in determining the absolute pH value of the mitochondria and recorded the ETC-uncoupler-stimulated pH shift with a precision of 0.1 unit. Thus the scientists showed that a single GFP with alkaline-shifted pKa can act as a high-precision indicator that can be used in a specific pH range. The work is published in the International Journal of Molecular Sciences. Learn more
Hydrophobic Rose Bengal derivatives as photosensitizing antiviral agents
Rose Bengal (BR) is an anionic xanthene dye that is actively used as a photosensitizer, mainly for antibacterial and antitumor photodynamic therapy. The use of BR and its derivatives for virus inactivation has not been comprehensively studied. A team of scientists from the Department of functioning of living systems IBCh RAS in collaboration with colleagues from other Russian Institutes used a synthetic approach based on the successful design of photosensitizing antivirals to obtain BR derivatives for virus photoinactivation. A number of N-alkyl-substituted derivatives with the same 1O2 generation efficiency but completely different activity against SARS-CoV-2, CHIKV, and HIV have been synthesized and studied. Several compounds have activities in the submicromolar-subnanomolar ranges and high selectivity indices. The synthesized compounds are promising candidates for the development of inactivated vaccines. The work was published in Biomolecules (IF = 6.064).