Ferritin-based fusion protein shows octameric deadlock state of self-assembly.

Ferritin is a universal protein complex responsible for iron perception in almost all living organisms and has applications from fundamental biophysics to drug delivery and structure-based immunogen design. Different platforms based on ferritin share similar technological challenges limiting their development - control of self-assembling processes of ferritin itself as well as ferritin-based chimeric recombinant protein complexes. In our research, we studied self-assembly processes of ferritin-based protein complexes under different expression conditions. We fused a ferritin subunit with a SMT3 protein tag, a homolog of human Small Ubiquitin-like Modifier (SUMO-tag), which was taken to destabilize ferritin 3-fold channel contacts and increase ferritin-SUMO subunits solubility. We first obtained the octameric protein complex of ferritin-SUMO (8xFer-SUMO) and studied its structural organization by small-angle X-ray scattering (SAXS). Obtained SAXS data correspond well with the high-resolution models predicted by AlphaFold and CORAL software of an octameric assembly around the 4-fold channel of ferritin without formation of 3-fold channels. Interestingly, three copies of 8xFer-SUMO do not assemble into 24-meric globules. Thus, we first obtained and structurally characterized ferritin-based self-assembling oligomers in a deadlock state. Deadlock oligomeric states of ferritin extend the known scheme of its self-assembly process, being new potential tools for a number of applications. Finally, our results might open new directions for various biotechnological platforms utilizing ferritin-based tools.

In silico studies of the open form of human tissue transglutaminase.

Human tissue transglutaminase (tTG) is an intriguing multifunctional enzyme involved in various diseases, including celiac disease and neurological disorders. Although a number of tTG inhibitors have been developed, the molecular determinants governing ligand binding remain incomplete due to the lack of high-resolution structural data in the vicinity of its active site. In this study, we obtained the complete high-resolution model of tTG by in silico methods based on available PDB structures. We discovered significant differences in the active site architecture between our and known tTG models, revealing an additional loop which affects the ligand binding affinity. We assembled a library of new potential tTG inhibitors based on the obtained complete model of the enzyme. Our library substantially expands the spectrum of possible drug candidates targeting tTG and encompasses twelve molecular scaffolds, eleven of which are novel and exhibit higher binding affinity then already known ones, according to our in silico studies. The results of this study open new directions for structure-based drug design of tTG inhibitors, offering the complete protein model and suggesting a wide range of new compounds for further experimental validation.

Disjunct habitat of cryptic Terebellides (Annelida, Trichobranchidae) species shows a phylogenetic link between polychaetes from the White and the North Seas.

Understanding the distribution and biodiversity of marine species is crucial for developing effective conservation strategies and maintaining the health of global ecosystems. Advancements in molecular data utilization have significantly improved our understanding of biodiversity within the genus Terebellides. In this study, we conducted a phylogenetic analysis on polychaete samples from the Kandalaksha Bay, White Sea, revealing their affiliation with a putative undescribed species of the genus Terebellides found in two locations of the North Sea. Interestingly, this species was not detected in the Norwegian and Barents Seas, leading us to propose a disjunct distribution scenario for this Terebellides species. This unique distribution pattern might be attributed to the succession of polychaetes by new species, facilitated by the Gulf Stream and a climate change role in driving shifts in species' ranges and altering marine ecosystem dynamics.

Unusual features of the c-ring of F1FO ATP synthases.

Membrane integral ATP synthases produce adenosine triphosphate, the universal "energy currency" of most organisms. However, important details of proton driven energy conversion are still unknown. We present the first high-resolution structure (2.3 Å) of the in meso crystallized c-ring of 14 subunits from spinach chloroplasts. The structure reveals molecular mechanisms of intersubunit contacts in the c14-ring, and it shows additional electron densities inside the c-ring which form circles parallel to the membrane plane. Similar densities were found in all known high-resolution structures of c-rings of F1FO ATP synthases from archaea and bacteria to eukaryotes. The densities might originate from isoprenoid quinones (such as coenzyme Q in mitochondria and plastoquinone in chloroplasts) that is consistent with differential UV-Vis spectroscopy of the c-ring samples, unusually large distance between polar/apolar interfaces inside the c-ring and universality among different species. Although additional experiments are required to verify this hypothesis, coenzyme Q and its analogues known as electron carriers of bioenergetic chains may be universal cofactors of ATP synthases, stabilizing c-ring and prevent ion leakage through it.

Spectroscopic study of low temperature interactions in Sm-mesogenic cyanophenyl co-condensates.

The IR- and UV-Vis spectroscopic study of samarium-mesogenic 4-pentyl-4'-cyanobiphenyl low temperatures co-condensates was made in temperature range 90-300 K. Two labile complexes with different metal/ligand ratio of 1:2 and 1:1 were found. They were characterized by methods of IR- and UV-spectroscopy. The solid state transformation of complex Sm(5CB)2 to Sm(5CB) was shown to take place at 170-210 K. The kinetics of the process revealed a wide distribution of complex reactivity and of reaction activation energy.

[Chemical ribonucleases. 2. Design and hydrolytic properties RNase mimetics based on diazabicyclo[2.2.2]octane with various positive charges]. / Khimicheskie ribonucleazy. 2. Dizain i gidroliticheskie svoistva RNKaza-mimetikov na osnove diazabitsiklo[2.2.2]oktana s razlichnym chislom polozhitel'nykh zariadov.

A procedure was proposed allowing one to synthesize RNA mimics on the basis of conjugates of diazabicyclo[2.2.2]octane with imidazole bearing a varying number of positive charges (nDm series, where n is the number of positive charges at neutral pH, m is the code of an imidazole-containing fragment of the catalytic domain: 1, histamine; 2, histidine methyl ester). The hydrolytic activity of six compounds of this series was studied under physiological conditions using in vitro transcript of human mitochondrial tRNA(Lys) as a substrate. It was shown that the rate of RNA hydrolysis with nDm conjugates rises with an increase in the number of positive charges: an approximately 30-fold acceleration of hydrolysis was observed with an increase in the total charge of the construct from +2 to +4.

[Synthetic ribonucleases. 1. Synthesis and properties of conjugates, containing an RNA-binding fragment based on lysine residues and an RNA hydrolyzing fragment, bearing an imidazole residue]. / Sinteticheskie ribonukleazy. 1. Sintez i svoistva kon''iugatov, soderzhashchikh RNK-sviazyvaiushchii fragment na osnove ostatkov lizina i RNK-gidrolizuiushchii fragment, nesushchii ostatok imidazola.

A series of RNA-hydrolyzing constructions was synthesized on the basis of peptide-like molecules containing residues of L-lysine, histamine and histidine methyl ester. These were shown to hydrolyze RNA effectively at neutral pH values. The in vitro transcript of tRNA(Lys) from human mitochondria and a tRNA-like fragment of RNA of Turnip Yellow Mosaic Virus were used in the experiments. Our chemical RNases quantitatively depolymerize some definite sequences (CA > or = UA > CG >> UC, CC, or CU) in both RNA molecules under optimum conditions. Moreover, no other sites were affected and no statistical hydrolysis was observed even after prolonged RNA incubation with the compounds of this series. The depolymerization rate of the RNA substrates exhibits a complex dependence on the concentration of ions of monovalent metals and on the concentration of the artificial ribonucleases.

[Changes in the immunotropic activity of neutrophilokins in the course of experimental staphylococcal infection]. / Izmenenie immunotropnoi aktivnosti neitrofilokinov v techenie éksperimental'noi stafilokokkovoi infektsii.

The influence of the products secreted by activated neutrophils (neutrophilokins) of mice, both intact and infected with staphylococci, on the activity of mouse spleen cells in the graft-versus-host reaction, immune response to sheep red blood cells and the antigen-presenting function of peritoneal macrophages was studied. Neutrophilokins of intact mice stimulated the activity of immunocompetent cells. Neutrophilokins obtained from infected mice on day 3 after infection produced an immunosuppressing effect. On day 7 after infection the immunostimulating activity of neutrophils was restored and showed practically no difference from the normal level.

[The effect of the peptide fractions of neutrophilokines on the immune response of mice infected with Staphylococcus aureus]. / Vliianie peptidnykh fraktsii neitrofilokinov na immunyi otvet myshei, zarazhennykh Staphylococcus aureus.

The influence of immunostimulating and immunosuppressing neutrophilokine fractions on the immune response of mice with staphylococcal infection has been studied. When injected into mice with staphylococcal infection, the immunostimulating fraction of the supernatants of activated neutrophils has been found to restore the activity of the immune system of the infected animals. The secretory products of intact neutrophils do not change or decrease the capacity of the animals for immune response under the conditions of the infectious process.

[A comparative study of immediate and long-term results of the treatment in cancer of the distal part of the stomach]. / Sravnitel'naia otsenka blizhaishikh i otdalennykh rezul'tatov lecheniia raka distal'nogo otdela zheludka.

Treatment results were studied in 117 cases of cancer of the distal part of the stomach; the patients had undergone subtotal resection. Postoperative lethality after Hofmeister-Finsterer's resection was 15.1%, after valve anastomosis-5.9% (overall lethality-8.3%). Postoperatively, patients with valve anastomosis did better and suffered surgery-related functional disorders less frequently than those treated after Hofmeister-Finsterer. 104 (97.2%) patients were followed up. Five-year survival was 45.2%; ten-year-32.2%.

[The role of the dispensary care of patients with dyshormonal breast diseases in the early detection of cancer]. / Rol' dispanserizatsii bol'nykh s disgormonal'nymi zabolevaniiami molochnykh zhelez v rannem vyiavlenii raka.

The results of regular check-ups of 154 patients with dyshormonal pathology of the breast are discussed. 24.2% of patients were cured. Cancer was detected in 11.3%, with 84.4% of tumors being at early stages. It was concluded that patients with dyshormonal pathology be examined every 3 months.

[Cancer of the gastric stump and its prevention]. / Rak kul'ti zheludka i ego profilaktika.

The paper deals with an evaluation of the condition of 216 cases of stomach resection of ulcer after Hofmeister-Finsterer and using valve anastomosis. Cancer of stomach stump was observed in cases of resection performed after Hofmeister-Finsterer but did not occur in those of valve anastomosis. Postresection gastritis appeared to be more pronounced in the former cases. Sanation of bile ducts proved to be an important factor in prevention of postresection complications. A reflux anastomosis was shown to be the best method of prevention of stump gastritis. Cases of stomach resection for ulcer should be followed up during the entire survival time after operation.

[Comparative evaluation of late results of the Hoffmeister-Finsterer gastrectomy and the method of valve anastomoses in peptic ulcer]. / Sravnite'lnaia otsenka otdalennykh rezu'ltatov rezektsii zheludka pri iazvennoi bolezni po Gofmeisteru-Finstereru i s sozdaniem klapannykh anastomozov.

Comparative assessment of the remote results of Hoffmeister-Finsterer gastrectomy with creation of valve anastomoses has demonstrated rare occurrence of postoperative complications owing to anastomoses. The operation is simple as concerns operative techniques and can be recommended as operation of choice in the treatment of peptic ulcer.

[Immediate and long-term results of the treatment in cancer of the large intestine]. / Blizhaishie i otdalennye rezul'taty lecheniia raka tolstoi kishki.

Operative treatment of 200 patients with carcinoma of the rectum is analysed. Planned operations were conducted on 101 patients, postoperative mortality was 7.8%. Surgery was undertaken in 93 patients with acute intestinal obstruction, postoperative mortality was 15.05%. Changes of the policy of treatment of patients with acute intestinal obstruction reduced postoperative mortality. Five-year survival was 67.1%.