We showed in this work that AtxA, a snake venom neurotoxic sPLA2, and PDI interact also in living rat PC12 cells. Atx and PDI co-localize these cells. We constructed a three-dimensional model of the complex between Atx and PDI as well as mammalian sPLA2s and PDI. By heterologous competition experiments we validated the model of the complex. Our results suggest a role of PDI in the (patho)physiology of some snake venom and mammalian sPLA2s by assisting the retrograde transport of these molecules from the cell surface. The sPLA2–PDI model constitutes a valuable tool to facilitate further insights into this process and into the (patho)physiology of sPLA2s in relation to their action intracellularly.
COBISS.SI-ID: 28439079
In the field of communication between cellular organelles, which is currently one of the focal in cell biology, we demonstrated a new way of connection between mitochondria and peroxisomes that relies the ERMES complex and the Pex11 protein. Our work received a high attention from researcher in the field and opened a way also to some other until now non-conventional views about organization of eukaryotic cells.
COBISS.SI-ID: 28442663
This review summarizes the so far obtained knowledge on distribution, structure and possible applications of aegerolysin proteins deriving from fungi. The emphasize is given to already described, and other potentially interesting biotechnological and biomedical applications of these proteins, which may serve as (i) markers to detect and label specific membrane lipids; (ii) biomarkers of fungal exposure (where their genes can serve as targets for detection of fungi and their progression during infectious diseases, while antibodies against aegerolysins can also be raised as immunodiagnostic tools); (iii) species-determination tool for fungal phytopathogen isolates in terms of some closely related species; and (iv) strong promoters that regulate aegerolysin genes can promote secretion of heterologous proteins from fungi and have been successfully applied in simultaneous multigene expression techniques.
COBISS.SI-ID: 3264591
Cholesterol content can distinctly vary between normal and cancer cells, being elevated in cancer cells. In presented work we evaluated the effects of cholesterol sequestration with methyl-β-cyclodextrin (MCD) and pore-formation with ostreolysin A/pleurotolysin B (OlyA/PlyB) protein complex that bind to the cholesterol/ sphingomyelin-rich membrane domains, on viability of the urothelial cancer and normal urothelial cells. Cholesterol content was strongly correlated with cancerous transformation, as being the highest in T24 cells, presenting high grade invasive carcinoma, and lowest in normal urothelial cells. MCD treatment induced prominent cell death of T24 cells, whereas OlyA/PlyB treatment resulted in a large decrease in viability of the low-grade, noninvasive RT4 carcinoma cells. Biochemical and electron microscopy analyses revealed that MCD and OlyA/PlyB induce necrotic cell death in both types of cancer cells while the viability of normal porcine urothelial cells was not significantly affected by MCD, and not at all affected by OlyA/PlyB. The increase of cholesterol content and the increase of cholesterol/ sphingomyelin-rich membrane domains in urothelial cancer cells thus constitute a selective therapeutic target for the elimination of urothelial cancer cells.
COBISS.SI-ID: 3572559
VaF1 was purified from nose-horned viper. This snake venom metalloproteinase (SVMP) was not hemorrhagic although it degraded some components of the extracellular matrix in vitro. VaF1 hydrolysed several plasma proteins involved in blood coagulation therefore it is expected to be an anticoagulant. VaF1 is an acidic, single-chain glycoprotein of 49.7 kDa. The complete amino acid sequence of the precursor of VaF1 was deduced by cloning and sequencing its cDNA. Structurally, VaF1 is a typical P-IIIa subclass SVMP. Interestingly, VaF1 was not recognised by antiserum against the whole venom, so it may contribute to post-serotherapy complications, such as ineffective blood coagulation, in the envenomed patient.
COBISS.SI-ID: 28236839