Biology subjects

Rogachev, A.

Publications and source records attributed to Rogachev, A..

6 recordsLinked to original sources

bioRxiv2026

Structure of a dodecameric double-ferritin-fold protein from an Asgard archaeon

Ferritins are ubiquitous iron homeostasis proteins found across the tree of life that form conserved 24-subunit cages with octahedral (4-3-2) symmetry. New types of ferritins and ferritin-like proteins are being continuously discovered, such as mini-bacterioferritins, which form smaller shells of 12 subunits, and double-ferritin-fold proteins, which act as ferroxidases but do not form shells. Here, we describe double-ferritin-fold proteins from Asgard archaea, dubbed dFTNs, and determine Cryo-EM structure of a representative from Candidatus Heimdallarchaeum endolithica. The protein forms a dodecameric shell with tetrahedral (2-3) symmetry. N-terminal (NTD) and C-terminal (CTD) domains are bridged by an ordered linker and are related by two-fold rotational pseudosymmetry. C-terminal -helix (helix E) that forms the four-fold channel in classic ferritins is repositioned to be the helix 2 out of 5 ferritin domain -helices in dFTN, with two such helices from NTD and two helices from CTD forming a pseudo-four-fold symmetry structural element. Four three-fold channels are formed by NTDs, and four other such channels are formed by CTDs. The overall arrangement of dFTN ferritin domains is similar to that of protomers in classic ferritin shells. Altogether, our findings expand the range of known ferritin family proteins and provide insight into Asgard archaea iron metabolism.

biophysics↗

bioRxiv2026

EEG correlates of auditory rise time processing: A systematic review

Rise time (RT) is considered to be one of the most significant acoustical characteristics of auditory speech stimuli. A substantial amount of data has been accumulated on the neurophysiological mechanisms of RT processing under different conditions and in different groups of people, but these data have not been systematised. This review focuses on studies that have investigated electroencephalographic (EEG) markers of RT sensitivity. The present literature search was conducted according to the PRISMA statement in PubMed, Web of Science and APA PsychInfo databases. The resultant review comprised 37 studies that considered diverse aspects of RT processing. The review describes the main stimulation parameters affecting electrophysiological markers of RT processing reflected in different components of event-related potentials, brainstem responses and cortical rhythmic activity. The main finding of this review is that the rise time prolongation leads to a decrease in the amplitude of the main ERP components and an increase in their latencies. However, the sensitivity of the EEG markers varied with the earliest components tracking the subtle difference (few tens of microseconds), while the later components coding the larger one (up to 500 ms). Nevertheless, the observed effects may vary and depend on some aspects of the experimental paradigm, age of participants and speech-related problems. Future research may benefit by addressing understudied clinical groups and ERP components such as P1 and N2, dominated in children.

neuroscience↗

bioRxiv2025

Unveiling the Molecular Architecture of Candida auris Ribosome

Candida auris is an emerging multidrug-resistant fungal pathogen causing life-threatening invasive candidiasis and bloodstream infections (candidemia), posing significant global health challenges. Despite its importance, the protein translation in pathogenic fungi is poorly characterized. Using cryo-electron microscopy and single-particle reconstruction, we resolved high-resolution structures of the 80S ribosome from C. auris in its vacant state and in complexes with three inhibitors: cycloheximide (CHX), blasticidin-S (BLS), and geneticin (G418). We uncovered a unique substitution of a key nucleotide in the P-site of the small ribosomal subunit (C1160 in C. auris), which may influence ribosome-tRNA interactions and translation fidelity. Comparative analysis of ribosome inhibitor interactions showed that resistance to CHX was observed in only two Candida species examined, while BLS binding displayed no significant differences between C. auris and S. cerevisiae, although C. auris was more sensitive to it. We identified that G418 exhibits promiscuous binding across multiple nonspecific sites, yet its primary interaction site at the decoding center remains highly conserved among Candida species. These findings provide a previously uncharacterized structure of the C. auris ribosome, highlighting novel features that may be leveraged for the development of targeted antifungal therapies to combat multidrug resistance. These insights not only enhance our understanding of ribosomal inhibitor interactions but also suggest potential biomarkers for predicting antifungal susceptibility in clinical applications.

molecular biology↗

bioRxiv2022

Structural basis for receptor selectivity and inverse agonism in S1P5 receptors

The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PR) - S1P1-5. S1P5 is predominantly expressed in nervous and immune systems, regulating the egress of natural killer cells from lymph nodes and playing a role in immune and neurodegenerative disorders, as well as carcinogenesis. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which leads to side effects. In this article, we describe a 2.2 [A] resolution room temperature crystal structure of the human S1P5 receptor in complex with a selective inverse agonist determined by serial femtosecond crystallography (SFX) at the Pohang Accelerator Laboratory X-Ray Free Electron Laser (PAL-XFEL) and analyze its structure-activity relationship data. The structure demonstrates a unique ligand-binding mode, involving an allosteric subpocket, which clarifies the receptor subtype selectivity and provides a template for structure-based drug design. Together with previously published S1PR structures in complex with antagonists and agonists, the new S1P5-inverse agonist structure sheds light on the activation mechanism and reveals structural determinants of the inverse agonism in the S1PR-family.

biophysics↗

bioRxiv2020

Metabolic fate of human immunoactive sterols in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection is among top ten causes of death worldwide, and the number of drug-resistant strains is increasing. The direct interception of human immune signaling molecules by Mtb remains elusive, limiting drug discovery. Oxysterols and secosteroids regulate both innate and adaptive immune responses. Here we report a functional, structural, and bioinformatics study of Mtb enzymes initiating cholesterol catabolism and demonstrated their interrelation with human immunity. We show that these enzymes metabolize human immune oxysterol messengers. Rv2266, the most potent among them, can also metabolize vitamin D3 (VD3) derivatives. High-resolution structures show common patterns of sterols binding and reveal a site for oxidative attack during catalysis. Finally, we designed a compound that binds and inhibits three studied proteins. The compound shows activity against Mtb H37Rv residing in macrophages. Our findings contribute to molecular understanding of suppression of immunity and suggest that Mtb has its own transformation system resembling the human phase I drug-metabolizing system.Competing Interest StatementA.Gi. and E.S. are employees of MT-Medicals LLC. The other authors declare no competing interests.View Full Text

biochemistry↗

bioRxiv2019

High Resolution Structural Insights into Heliorhodopsin Family

Rhodopsins are the most abundant light-harvesting proteins. A new family of rhodopsins, heliorhodopsins (HeRs), was recently discovered. In opposite to the known rhodopsins their N-termini face the cytoplasm. HeRs structure and function remain unknown. We present structures of two HeR-48C12 states at 1.5 [A] showing its remarkable difference from all known rhodopsins. Its internal extracellular part is completely hydrophobic, while the cytoplasmic part comprises a cavity (active site), surrounded by charged amino acids and containing a cluster of water molecules, presumably being a primary proton acceptor from the Schiff base. At acidic pH a planar triangle molecule (acetate) is present in the active site which demonstrated its ability to maintain such anions as carbonate or nitrate. Structure-based bioinformatic analysis identified 10 subfamilies of HeRs suggesting their diverse biological functions. The structures and available data suggest an enzymatic activity of HeR-48C12 subfamily and their possible involvement into fundamental redox biological processes.

biophysics↗