Institute of
bioorganic chemistry

Researchers from the Group of in silico analysis of membrane proteins structure and the Laboratory of biomolecular modeling IBCH RAS in collaboration with Russian and foreign colleagues have suggested the molecular basis of fatty acid selectivity in the human DHHC family of protein acyltransferases (hDHHC). Based on calculated large set of molecular dynamics simulations it was demonstrated that selectivity of hDHHC20 towards palmitoyl (C16) is predetermined by the teepee-like shape of the enzyme: there is a bottleneck in the middle of the transmembrane segment, that regulates the positioning of reacting groups of both molecules. This hypothesis enabled the prediction of the hDHHC20 mutant V185G with a presumed selectivity shift towards C18. The study is published in the International Journal of Molecular Sciences.

The rapid elimination of systemically administered drug nanocarriers by the mononuclear phagocyte system (MPS) compromises nanomedicine delivery efficacy. Scientists from the Laboratory of molecular immunology IBCh RAS in collaboration with Russian and Australian colleagues have developed a modern, effective and biocompatible agent for the temporary MPS blockade based on nanosized ferrihydrite particles that mimic endogenous iron associated with ferritin. Preliminary administration of ferrihydrite particles coated with carboxymethyl-dextran increased the blood circulation time of magnetic particles by 9 times and their targeted delivery to the tumor by 24 times, and also showed low toxicity. The work was published in the International Journal of Pharmaceutics.

In a new study, researchers from the Laboratory of molecular bases of embryogenesis, Institute of Bioorganic Chemistry, Russian Academy of Sciences, demonstrated the versatility of the previously discovered mechanism of maternal genes mRNA destabilization caused by an interaction between the cytoskeletal protein Zyxin and the mRNA-binding factor Ybx1, showing that the same mechanism governs the retinoic acid signaling pathway during early embryonic development. The work was published in the International Journal of Molecular Sciences. Learn more

CRISPR-Cas systems are widely recognized as a genome editing tool. In nature, these systems play the role of bacterial adaptive immunity against bacteriophages and other mobile genetic elements. It is generally believed that mutations are responsible for overcoming such defenses. In a study led by Konstantin Severinov involving several groups from Russia, the United States and Chile, it was found that even with a fully functional CRISPR-Cas and an unmutated target sequence, the plasmid can persist for many generations in a small subpopulation of E. coli cells. A model system using fluorescent proteins made it possible to trace the activity of the CRISPR-Cas system at the level of single living bacterial cells. The work was published in the Proceedings of the National Academy of Sciences of USA.

Scientists from the Laboratory of proteolytic enzyme chemistry IBCh RAS in collaboration with colleagues from National Cancer Institute (Frederick, USA) published the review on structural studies of ATP-dependent Lon proteases – key components of the protein quality control system. Targets of Lon proteases are mutant, damaged and some regulatory proteins. Three subfamilies have been identified in the Lon family, whose representatives are formed by ATPase domains of the AAA+ protein superfamily, serine–lysine peptidases and differing inactive extra domains. Barrel-shaped hexamers of Lon proteases bind protein targets, unfold them and translocate to an internal degradation chamber, where they undergo proteolysis. 3D analysis was used to obtain data on the structure of both individual domains and multi-domain fragments of different subfamilies’ Lon proteases. The use of cryo-electron microscopy made it possible to solve the structures of a number of full-length Lon proteases, as well as to describe the state of the enzymes at different stages of the catalytic cycle. The review is published in the Journal of Molecular Biology.