DSSR-enabled G4 identification/annotation

Summary information and primary citation

PDB-id: 6k84
Class: RNA
Method: NMR
Summary: Structure of anti-prion RNA aptamer
Reference: Mashima T, Lee JH, Kamatari YO, 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. doi: 10.1038/s41598-020-61966-4.
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, UUUU, parallel, 4+0, 2(-P-P-P), coaxial interfaces: 5'/5'

Cartoon-block schematics in six views (download the tarball)

List of 4 G-tetrads

 1 glyco-bond=---- sugar=-3-3 groove=---- planarity=0.364 type=bowl   O+ nts=4 GGGG A.G1,A.G4,A.G7,A.G10
 2 glyco-bond=---- sugar=---- groove=---- planarity=0.385 type=bowl   O+ nts=4 GGGG A.G2,A.G5,A.G8,A.G11
 3 glyco-bond=---- sugar=-3-. groove=---- planarity=0.193 type=other  O+ nts=4 GGGG A.G14,A.G17,A.G20,A.G23
 4 glyco-bond=---- sugar=---3 groove=---- planarity=0.390 type=other  O+ nts=4 GGGG A.G15,A.G18,A.G21,A.G24

List of 1 G4-helix

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-tetrads, INTRA-molecular, with 2 stems

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

List of 2 G4-stems

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-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 2(-P-P-P)

 1  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major O+ nts=4 GGGG A.G1,A.G4,A.G7,A.G10
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ 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=-- sugar=-- nts=2 GG A.G1,A.G2
  strand#2  U RNA glyco-bond=-- sugar=3- nts=2 GG A.G4,A.G5
  strand#3  U RNA glyco-bond=-- sugar=-- nts=2 GG A.G7,A.G8
  strand#4  U RNA glyco-bond=-- sugar=3- 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

Download PDB file
Interactive view in 3Dmol.js

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

 1  glyco-bond=---- sugar=-3-. groove=---- WC-->Major O+ nts=4 GGGG A.G14,A.G17,A.G20,A.G23
 2  glyco-bond=---- sugar=---3 groove=---- WC-->Major O+ 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=-- sugar=-- nts=2 GG A.G14,A.G15
  strand#2  U RNA glyco-bond=-- sugar=3- nts=2 GG A.G17,A.G18
  strand#3  U RNA glyco-bond=-- sugar=-- nts=2 GG A.G20,A.G21
  strand#4  U RNA glyco-bond=-- sugar=.3 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