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Klimenko, V.

Publications and source records attributed to Klimenko, V..

2 recordsLinked to original sources

The Paulinella chromatophore transit peptide part2 adopts a structural fold similar to the γ-glutamyl-cyclotransferase fold

The chromatophores of the cercozoan amoeba Paulinella are photosynthetic organelles that evolved from a cyanobacterial endosymbiont. Many nucleus-encoded chromatophore-targeted proteins carry unusual N-terminal targeting signals termed crTPs. The crTPs are bipartite. Whereas crTPpart1 that likely mediates trafficking through the secretory pathway is cleaved off during import, crTPpart2 remains attached to its cargo protein. The function of crTPpart2 is unknown. To contribute to unravel the functional role of crTPpart2, here we elucidated the structures of crTPpart2 from two different chromatophore-targeted proteins by X-ray crystallography at [~]2.3 [A] resolution. Interestingly, the crTPpart2 of both proteins adopts a structural fold. Both structures share a conserved structured core and a flexible N-terminal arm. The structured core resembles proteins of the {gamma}-glutamyl cyclotransferase superfamily within which crTPpart2 structures form a novel protein (sub)-family. The proposed catalytic center typical for proteins with cyclotransferase activity is not conserved in crTPpart2. A Cys pair that is conserved in crTPpart2 of many chromatophore-targeted proteins has been captured as disulfide bridge. Together, our data suggests that chromatophore-targeted proteins are imported in their folded state and that the fold adopted by crTPpart2 plays a functional role during import. The characterization of its structure and flexibility provides important steps towards elucidating this novel protein translocation mechanism.

microbiology↗

Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cells in vitro

Gene silencing through RNA interference (RNAi) is a promising therapeutic approach for a wide range of disorders, including cancer. Non-viral gene therapy, using specific siRNAs against BCR-ABL, can be a supportive or alternative measure to traditional chronic myeloid leukemia (CML) tyrosine kinase inhibitor (TKIs) therapies, given the prevalence of clinical TKI resistance. The main challenge for such approaches remains the development of the effective delivery system for siRNA tailored to the specific disease model. The purpose of this study was to examine and compare the efficiency of endosomolytic cell penetrating peptide (CPP) EB1 and PEG2000-decorated cationic liposomes composed of polycationic lipid 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for anti-bcr-abl siRNA delivery into the K562 human CML cell line. We show that both EB1 and 2X3-DOPE-DSPE-PEG2000 (0.62% mol.) liposomes effectively deliver siRNA into K562 cells by endocytic mechanisms, and the use of liposomes leads to more effective inhibition of expression of the targeted gene (BCR-ABL) and cancer cell proliferation. Taken together, these findings suggest that PEG-decorated cationic liposomes mediated siRNA delivery allows an effective antisense suppression of certain oncogenes, and represents a promising new class of therapies for CML.

molecular biology↗