DSSR-derived G-quadruplex features in PDB entry 6k84
Poster "DSSR-Enabled Automatic Identification and Annotation of G-quadruplexes in the PDB" presented at the RNA2020 online meeting
Citation: before a paper dedicated to the DSSR-G4 module comes out, please cite the 2015 DSSR paper published in Nucleic Acids Research.
- Structure of anti-prion RNA aptamer
- Mashima, T., Lee, J.H., Kamatari, Y.O., Hayashi, T., Nagata, T., Nishikawa, F., Nishikawa, S., Kinoshita, M., Kuwata, K., Katahira, M.: (2020) "Development and structural determination of an anti-PrPCaptamer that blocks pathological conformational conversion of prion protein." Sci Rep, 10, 4934-4934.
- Prion diseases comprise a fatal neuropathy caused by the conversion of prion protein from a cellular (PrPC) to a pathological (PrPSc) isoform. Previously, we obtained an RNA aptamer, r(GGAGGAGGAGGA) (R12), that folds into a unique G-quadruplex. The R12 homodimer binds to a PrPC molecule, inhibiting PrPC-to-PrPSc 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 PrPSc (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.
- G4 notes
- 4 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack · 2(-P-P-P), parallel(4+0), UUUU · coaxial interfaces: 5'/5'
1 glyco-bond=---- groove=---- planarity=0.364 type=bowl nts=4 GGGG A.G1,A.G4,A.G7,A.G10 2 glyco-bond=---- groove=---- planarity=0.385 type=bowl nts=4 GGGG A.G2,A.G5,A.G8,A.G11 3 glyco-bond=---- groove=---- planarity=0.193 type=other nts=4 GGGG A.G14,A.G17,A.G20,A.G23 4 glyco-bond=---- groove=---- planarity=0.390 type=other nts=4 GGGG A.G15,A.G18,A.G21,A.G24
Helix#1, 4 G-tetrad layers, INTRA-molecular, with 2 stems
Stem#1, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)
Stem#2, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)
1 G4 helix#1 contains 2 G4 stems: [#1,#2] [5'/5']