Summary information [schematics · tetrads · helices · stems · costacks · homepage]

PDB-id
6k84
Class
RNA
Method
NMR
Summary
Structure of anti-prion RNA aptamer
Reference
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.
Abstract
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'

Base-block schematics in six views [summary · tetrads · helices · stems · costacks · homepage]

PyMOL session file PDB file View in 3Dmol.js

List of 4 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 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

List of 1 G4-helix [summary · schematics · tetrads · stems · costacks · homepage]

In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.

Helix#1, 4 G-tetrad layers, INTRA-molecular, with 2 stems

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G2,A.G5,A.G8,A.G11
 2* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G1,A.G4,A.G7,A.G10
 3  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G23,A.G20,A.G17,A.G14
 4  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G24,A.G21,A.G18,A.G15
  step#1  mp(<<,backward) area=6.14  rise=3.41 twist=37.0
  step#2  mm(<>,outward)  area=24.05 rise=3.56 twist=7.3
  step#3  pm(>>,forward)  area=10.02 rise=3.27 twist=34.7
  strand#1 RNA glyco-bond=---- nts=4 GGGG A.G2,A.G1,A.G23,A.G24
  strand#2 RNA glyco-bond=---- nts=4 GGGG A.G5,A.G4,A.G20,A.G21
  strand#3 RNA glyco-bond=---- nts=4 GGGG A.G8,A.G7,A.G17,A.G18
  strand#4 RNA glyco-bond=---- nts=4 GGGG A.G11,A.G10,A.G14,A.G15

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3 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G2,A.G5,A.G8,A.G11
2* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G1,A.G4,A.G7,A.G10
step#1 mp(<<,backward) area=6.14 rise=3.41 twist=37.0

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 2* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G1,A.G4,A.G7,A.G10
3 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G23,A.G20,A.G17,A.G14
step#2 mm(<>,outward) area=24.05 rise=3.56 twist=7.3

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 3  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G23,A.G20,A.G17,A.G14
4 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G24,A.G21,A.G18,A.G15
step#3 pm(>>,forward) area=10.02 rise=3.27 twist=34.7

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List of 2 G4-stems [summary · schematics · tetrads · helices · costacks · homepage]

In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.

Stem#1, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G1,A.G4,A.G7,A.G10
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G2,A.G5,A.G8,A.G11
  step#1  pm(>>,forward)  area=6.14  rise=3.41 twist=37.0
  strand#1  U RNA glyco-bond=-- nts=2 GG A.G1,A.G2
  strand#2  U RNA glyco-bond=-- nts=2 GG A.G4,A.G5
  strand#3  U RNA glyco-bond=-- nts=2 GG A.G7,A.G8
  strand#4  U RNA glyco-bond=-- nts=2 GG A.G10,A.G11
  loop#1 type=propeller strands=[#1,#2] nts=1 A A.A3
  loop#2 type=propeller strands=[#2,#3] nts=1 A A.A6
  loop#3 type=propeller strands=[#3,#4] nts=1 A A.A9

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Stem#2, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G14,A.G17,A.G20,A.G23
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G15,A.G18,A.G21,A.G24
  step#1  pm(>>,forward)  area=10.02 rise=3.27 twist=34.7
  strand#1  U RNA glyco-bond=-- nts=2 GG A.G14,A.G15
  strand#2  U RNA glyco-bond=-- nts=2 GG A.G17,A.G18
  strand#3  U RNA glyco-bond=-- nts=2 GG A.G20,A.G21
  strand#4  U RNA glyco-bond=-- nts=2 GG A.G23,A.G24
  loop#1 type=propeller strands=[#1,#2] nts=1 A A.A16
  loop#2 type=propeller strands=[#2,#3] nts=1 A A.A19
  loop#3 type=propeller strands=[#3,#4] nts=1 A A.A22

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List of 1 G4 coaxial stack [summary · schematics · tetrads · helices · stems · homepage]

 1 G4 helix#1 contains 2 G4 stems: [#1,#2]  [5'/5']

List of 0 non-stem G4-loops (including the two closing Gs)