Press-room / Digest
A Uniquely Stable Trimeric Model of SARS-CoV-2 Spike Transmembrane Domain
Tools created at the Laboratory of Biomolecular Modelling IBCh RAS have been brought together into a computational framework to build a model of SARS-CoV-2 spike transmembrane domain (TMD). Apart from template-based modelling, the framework relies on the molecular hydrophobicity potential (MHP) analyser Platinum, dimer prediction utility PREDDIMER and the adjustment of ‘dynamic MHP portraits’ observed during molecular dynamics simulations. The final model, the only existing one taking into account the lipid environment and helical TMD packing principles, demonstrated phenomenal stability in a model membrane, both on its own and palmitoylated downstream, proving to be stabler than alternative models and a recent NMR structure. The results are published in the International Journal of Molecular Sciences. Learn more
Impact of Exogenous Application of Potato Virus Y-Specific dsRNA on RNA Interference, Pattern-Triggered Immunity and Poly(ADP-ribose) Metabolism in Potato Plants
Methods for inhibition of viral infection induced by spraying plants with preparations of specific double-stranded RNAs (dsRNAs) are currently being actively developed. Researchers from the Laboratory of functional genomics and plant proteomics, the Laboratory of Molecular Diagnostics and the Laboratory of Molecular Bases of Plant Stress Resistance of the Institute of Bioorganic Chemistry RAS studied the contribution of potato plant treatment with dsRNA against potato virus Y (dsRNA-PVY) to two dsRNA-induced plant defense mechanisms: specific RNA interference (RNAi) and non-specific pattern-triggered immunity (PTI). It has been shown that application of PVY dsRNA in potato plants induced accumulation of both small interfering RNAs (siRNAs), a hallmark of RNAi, and some gene transcripts related to PTI. The results are published in the International Journal of Molecular Sciences. Learn more
Proton transfer reactions in donor site mutants of ESR, a retinal protein from Exiguobacterium sibiricum
Microbial rhodopsins are integral membrane proteins that contain the retinal chromophore and perform light-dependent ion transport or other functions. The interest in them is largely explained by the perspectives for use in optogenetics in order to regulate the neuronal activity, including for the treatment of various diseases. A team of scientists from the Laboratory of protein engineering and the Group of nanobioengineering of the ICBh RAS has been studying the rhodopsin from Exiguobacterium sibiricum (ESR) for many years. The presence of a lysine residue at position 96 corresponding to the internal proton donor for the Schiff base distinguishes it from bacteriorhodopsin (BR), the most studied retinal protein. In a new study, carried out in collaboration with colleagues from other Russian and foreign institutions, authors have shown that Asp or Glu residues in this position effectively perform the function of a donor in the ESR molecule. However, the kinetics of the photocycle and charge transfer in mutants differ significantly from BR, indicating an alternative mechanism for reprotonation of the Schiff base in ESR. The results are published in the J Photochem Photobiol B.
SOX9 Protein in Pancreatic Cancer Regulates Multiple Cellular Networks in a Cell-Specific Manner
Pancreatic ductal adenocarcinoma is one of the most lethal cancers worldwide. It is hypothesized that the high level of pancreatic developmental factor SOX9 is necessary for the formation and maintenance of tumor phenotypes. Here authors showed that SOX9 downregulation leads to cell-specific changes in the expression levels of epithelial and mesenchymal protein markers and pancreatic developmental master genes. siSOX9 transfection led to a significant decrease in proliferative activity and to the activation of proapoptotic caspases in transfected cells. The acquired results demonstrate that the SOX9 protein exerts its multiple functions as a pleiotropic regulator of differentiation and a potential promoter of tumor growth. The research was performed at the Laboratory of human genes structure and functions and the Group of gene immuno-oncotherapy of the IBCh RAS and was published in Biomedicines journal.
ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model
ADGRL1 (Latrophilin 1), a receptor for α-latrotoxin from the black widow spider, can modulate neurotransmitter release in neurons, but so far no data directly linked it to a heritable condition. A team of scientists from the Laboratory of microfluidic technologies for biomedicine IBCh RAS in collaboration with colleagues from other Russian and foreign institutions showed that individuals heterozygous for different pathogenic variants of ADGRL1 display various neuro-psychiatric features, including developmental delay, intellectual disability, attention deficit/hyperactivity, autism spectrum disorders and epilepsy. In vitro, these pathogenic variants encode receptors with perturbed functions. Adgrl1 knockout mice have altered neurotransmitter release and deficient synapse formation in culture, and show neurological and developmental abnormalities similar to human conditions. The data demonstrate that ADGRL1 haploinsufficiency causes developmental, neurological and behavioral abnormalities in mice and humans, clearly linking ADGRL1 receptor to important CNS functions. The results are publushed in the American Journal of Human Genetics.