Neuroprotective activity of neuroglobin (Ngb) is presumably based on its redox interaction with cytochrome c (Cyt c), the mechanisms of which have not yet been elucidated. Authors developed a new methodological approach to study the electron transfer between heme proteins based on Raman spectroscopy. We studied the conformational changes in the Cyt c heme and the effect of the protein microenvironment of Cyt c and Ngb hemes on electron transfer between them using developed approach. Obtained data allowed us to propose a step-by-step mechanism of interaction between Ngb and Cyt c. Understanding the mechanisms of interaction between Ngb and Cyt c is necessary for future practical applications related to the therapy of neurodegenerative diseases.

A team of scientists with the participation of researchers from the Institute of Bioorganic Chemistry RAS has revealed the nature of the green pigment in the bush cricket Tettigonia cantans. It turned out that the bush cricket owes its protective coloration to a chromoprotein with a unique fold that contains two chromophores simultaneously. One of them is a yellow carotenoid, and the other is a blue bilin. The mixture of the two colors results in a bright green coloration, practically indistinguishable from grass and allowing the animal to cleverly hide. The work has been published in PNAS.

Researchers from Laboratory of Neuroreceptors and Neuroregulators and Laboratory of Biomolecular NMR-Spectroscopy of IBCh RAS, together with the Laboratory of Biological Testing of the BIBCh, isolated and characterized Ms13-1, a new peptide of the sea anemone Metridium senile with a unique 3D-structure and a pronounced selective effect on acid-sensing ion channels ASIC1a. Ms13-1 has a spatial fold named the "Cys-ladder" by the authors, and is a member of a novel structural class. In the nanomolar range, Ms 13-1 acts as a positive allosteric modulator of ASIC1a, and the injection of the peptide into the mouse hind paw causes pain, which is suppressed by the selective antagonist of ASIC1. The work was published in the FEBS Journal and was marked as the Editors' choice for the May issue.

Combinations of novel in vivo approaches allow to detail redox events with high spatiotemporal resolution in the brain tissues of laboratory animals. We demonstrated redox differences between neurons and astrocytes in damaged brain areas of rodents in vivo during ischemic stroke in model of middle cerebral artery occlusion in rats and photothrombosis model in mice. Using highly sensitive genetically encoded biosensor HyPer7 and a fiber-optic neurointerface technology, we demonstrated that astrocytes differ from neurons in elevated hydrogen peroxide levels in the ischemic brain area of rats. Raman microspectroscopy also revealed the overloading of the mitochondrial electron transport chain precisely in astrocytes in the brain tissues of awake mice during acute ischemia. The results are published in Antioxidants & Redox Signaling.

Age-related imbalance between synthesis and degradation of biomolecules in cells leads to the development of, among other, neurodegenerative diseases and diabetes. A decrease in autophagy, a process that is involved in degradation of damaged or dysfunctional cellular components, may contribute to this imbalance. Autophagy is regulated within cells through multiple signaling pathways, including the AMPK (AMP-activated protein kinase)-dependent pathway, which functions as a key sensor of changes in the cell's energy status. Researchers from the IBCh RAS, the A.N. Belozersky Institute of Physicochemical Biology of Moscow State University, the Patrice Lumumba Peoples' Friendship University of Russia, and other institutes assessed the ability of phenoxazine derivatives to activate this process. The lead compound demonstrated specific activation via the AMPK-dependent pathway and low cytotoxicity in three non-cancer cell lines. The work was published in Bioorganic Chemistry.

The staff of the Laboratory of Lipid Chemistry IBCh RAS, together with colleagues from Nizhny Novgorod State University and the Human Proteome Center of the Institute of Biomedical Chemistry, studied the effects of protein coronas formed in human blood plasma ex vivo on different liposomes carrying a colchicine analog. Today colchicine is considered as a possible treatment for cardiovascular complications. On a model of monocytes from human peripheral blood, the protein coronas have been shown to enhance the anti-inflammatory potential of liposomes. A particularly sharp effect was observed for liposomes bearing specific proteins, including minor ones in normal plasma.

A team of scientists from the Laboratory of Biomolecular NMR Spectroscopy at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, in collaboration with researchers from China, has made a breakthrough in understanding the function of Toll-like receptor 2 (TLR2), a key component of the innate immune system. Their study, published in FEBS Letters, reveals that TLR2 exhibits a previously unknown ability to bind zinc ions with high affinity and specificity. Toll-like receptors (TLRs) serve as the first line of defense in the immune system by recognizing pathogens and initiating immune responses. Despite extensive research, the precise molecular mechanisms governing TLR activation remain elusive. The newly identified zinc-binding capability of TLR2 provides fresh insights into its regulatory mechanisms. The researchers also identified specific amino acids essential for zinc coordination and TLR2 function, highlighting a potential link between zinc homeostasis and immune activation. These findings suggest that zinc plays a critical role in modulating TLR-mediated immune signaling, opening new avenues for research into immune system regulation and potential therapeutic applications.

A whole family of peptides with completely unexpected activity has been discovered in spider venom. These peptides inhibit mammalian purinergic receptors with high affinity and selectivity. A peptide called purotoxin-6 (PT6) from the venom of the crab spider Thomisus onustus inhibits P2X3 receptors, an important pharmacological target in a number of pain syndromes and chronic cough. PT6 has a compact fold and exhibits a potent analgesic effect in animal models of osteoarthritis and trigeminal neuralgia. At the same time, unlike small-molecule P2X3 ligands that are being developed as drugs, purotoxin does not cause dysgeusia, i.e., distortion of the sense of taste. Research on purotoxins began at the Institute of Bioorganic Chemistry some 20 years ago under the supervision of Academician Eugene Grishin and was successfully continued by Alexander Vassilevski. The results, unique on a global scale, were published in Molecular Therapy.

Potassium channels are one of the major players in the transduction of the nerve impulse, and mutations in their genes lead to neurological and cardiovascular diseases. The most important feature of K+-channels is their highest selectivity for K+ over Na+ and other cations. In the new work, members of the Group of in silico Analysis of Membrane Proteins Structure and the Laboratory of Molecular Instruments for Neurobiology analyzed all known 3D-structures of membrane proteins. As a result, the key principle of K+-channel selectivity filter architecture was confirmed: within it, oxygen atoms of the protein backbone are arranged in a chain of square antiprisms, replicating exactly the solvation geometry of the potassium ion. Distortion of the filter, for example during inactivation, is detected by the algorithm developed by the authors, which can be used for structural classification.

Preeclampsia is a serious pregnancy complication characterized by hypertension and multi-organ involvement in pregnant women. This condition occurs in 2–8% of all pregnancies and remains one of the leading causes of maternal and perinatal mortality. Despite decades of research, the exact mechanisms of its development are not fully understood, and existing therapeutic strategies remain only partially effective. A new study published by a team of Russian scientists led by Evgeny Knyazev, Polina Vishnyakova, Olga Lazareva, and Alexander Tonevitsky provides an overview of modern cellular models of preeclampsia and their potential in the search for new diagnostic and therapeutic approaches.