6k84

Structure of anti-prion RNA aptamer

spinqualitylabelsall models 6k84 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6k84 is a 1 chain structure with sequence from Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Prion diseases comprise a fatal neuropathy caused by the conversion of prion protein from a cellular (PrP(C)) to a pathological (PrP(Sc)) isoform. Previously, we obtained an RNA aptamer, r(GGAGGAGGAGGA) (R12), that folds into a unique G-quadruplex. The R12 homodimer binds to a PrP(C) molecule, inhibiting PrP(C)-to-PrP(Sc) conversion. Here, we developed a new RNA aptamer, r(GGAGGAGGAGGAGGAGGAGGAGGA) (R24), where two R12s are tandemly connected. The 50% inhibitory concentration for the formation of PrP(Sc) (IC50) of R24 in scrapie-infected cell lines was ca. 100 nM, i.e., much lower than that of R12 by two orders. Except for some antibodies, R24 exhibited the lowest recorded IC50 and the highest anti-prion activity. We also developed a related aptamer, r(GGAGGAGGAGGA-A-GGAGGAGGAGGA) (R12-A-R12), IC50 being ca. 500 nM. The structure of a single R12-A-R12 molecule determined by NMR resembled that of the R12 homodimer. The quadruplex structure of either R24 or R12-A-R12 is unimolecular, and therefore the structure could be stably formed when they are administered to a prion-infected cell culture. This may be the reason they can exert high anti-prion activity. Development and structural determination of an anti-PrP(C) aptamer that blocks pathological conformational conversion of prion protein.,Mashima T, Lee JH, Kamatari YO, Hayashi T, Nagata T, Nishikawa F, Nishikawa S, Kinoshita M, Kuwata K, Katahira M Sci Rep. 2020 Mar 18;10(1):4934. doi: 10.1038/s41598-020-61966-4. PMID:32188933 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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