Press-room / Digest
HSP70 Multi-Functionality in Cancer
Researchers from the Laboratory of Cell Interactions, IBCh RAS, together with colleagues from the Department of Immunology and the Department of Bioengineering of Moscow State University, in their work “HSP70 Multi-Functionality in Cancer” examined various functions of HSP70 in the Hallmarks of Cancer. This work emphasizes the importance of understanding the structure, functional cycle, conformational changes of HSP70 for the future development of effective anticancer therapy. Using molecular docking studies, the interaction of key HSP70 domains with various receptors has also been demonstrated. The work was published in Cells.
A 12-mer Peptide of Tag7 (PGLYRP1) Forms a Cytotoxic Complex with Hsp70 and Inhibits TNF-Alpha Induced Cell Death
Previously, a team of scientists from the Veterinary service and the Laboratory of bioengineering of neuromodulators and neuroreceptors demonstrated that the innate immunity protein Tag7 (PGRP-S, PGLYRP1) can interact with the TNFα receptor, TNFR1, and block the transduction of apoptotic signals through this receptor. A complex formed between the Tag7 protein and the major heat shock protein Hsp70 can activate TNFR1 receptor and induce tumor cell death via either apoptotic or necroptotic pathway. In this study, they show that a 12-mer peptide, designated 17.1, which was derived from the Tag7 protein, can be regarded as a novel TNFα inhibitor, also is able to form a cytotoxic complex with the heat shock protein Hsp70. Also, this new inhibitory 17.1 peptide demonstrates an anti-inflammatory activity in the complete Freund’s adjuvant (CFA)-induced autoimmune arthritis model in laboratory mice. It appears that the 17.1 peptide could potentially be used as an anti-inflammatory agent. The work is published in Cells.
The immune response to the vaccine is studied at the level of individual T-cells
The diverse repertoire of T-cells plays a key role in the adaptive immune response. Researchers from the Laboratory of Comparative and Functional Genomics in collaboration with IKMB (Kiel, Germany) and ENS (Paris, France) used high throughput sequencing of alpha/beta T-cell receptors (TCR) as well as single cell RNA sequencing to analyse the alterations in T-cell repertoire after primary and secondary vaccination against yellow fever. The response to the secondary vaccination is an order of magnitude weaker, but much faster than the primary one. More than 60% of all cytotoxic response could be focused on a single epitope of the yellow fever virus. Researchers characterized distinctive motifs in amino acid TCR sequences that are essential for the recognition of this immunodominant epitope. The study is published in eLife.
Unforeseen possibilities to investigate the regulation of polyamine metabolism revealed by novel C-methylated spermine derivatives
Scientists from IMB, the University of Eastern Finland, together with employees of the Laboratory of molecular design and synthesis of IBCh RAS, study the cellular functions of biogenic polyamines spermin and spermidin involved in the regulation of vital cellular functions including proliferation and differentiation. An original system of C-methylated spermin derivatives was created, whose interaction with polyamine metabolism enzymes can be regulated by moving the methyl group along the spermin backbone. The use of these compounds allows us to study the individual cellular effects of easily interconvertible and partially interchangeable spermin and spermidin, as well as the mechanisms of Antizyme (OAZ1)-mediated downregulation of polyamines - the main mechanism for maintaining polyamine homeostasis in the cell. The work was published in Journal of Medicinal Chemistry.
Are there specific antibodies against Neu5Gc epitopes in the blood of healthy individuals?
Human biosynthetic machinery only synthesizes N-acetylneuraminic acid (Neu5Ac), while the other mammals synthesize both it and N-glycolylneuraminic acid (Neu5Gc), i.e., the latter is a potential xeno-antigen for humans. At the same time, Neu5Ac from the eaten meat of animals is metabolically active and found in human glycans, so it was believed that humans have antibodies to Neu5Gca2-3Galb1-4GlcNAc. Researchers from the Laboratory of Carbohydrates IBCH RAS systematically studied the repertoire of antibodies from healthy donors and found (see Glycobiology) that they have practically no antibodies to this glycan. At the same time, antibodies to Neu5Gc-containing glycans were found in patients with multiple sclerosis (see Neurology: Neuroimmunology & Neuroinflammation), which may be a marker of this disease.