Summary information and primary citation

PDB-id
6e81
Class
RNA
Method
X-ray (2.721 Å)
Summary
Crystal structure of the corn aptamer in complex with tht
Reference
Sjekloca L, Ferre-D'Amare AR (2019): "Binding between G Quadruplexes at the Homodimer Interface of the Corn RNA Aptamer Strongly Activates Thioflavin T Fluorescence." Cell Chem Biol, 26, 1159. doi: 10.1016/j.chembiol.2019.04.012.
Abstract
Thioflavin T (ThT) is widely used for the detection of amyloids. Many unrelated DNAs and RNAs that contain G-quadruplex motifs also bind ThT and strongly activate its fluorescence. To elucidate the structural basis of ThT binding to G quadruplexes and its fluorescence turn-on, we determined its co-crystal structure with the homodimeric RNA Corn, which contains two G quadruplexes. We found that two ThT molecules bind in the dimer interface, constrained by a G quartet from each protomer into a maximally fluorescent planar conformation. The unliganded Corn homodimer crystal structure reveals a collapsed fluorophore-binding site. In solution, Corn must fluctuate between this and an open, binding-competent conformation. A co-crystal structure with another benzothiazole derivate, thiazole orange (TO), also shows binding at the Corn homodimer interface. As the bound ThT and TO make no interactions with the RNA backbone, their Corn co-crystal structures likely explain their fluorescence activation upon sequence-independent DNA and RNA G-quadruplex binding.
G4 notes
4 G-tetrads, 2 G4 helices, 2 G4 stems, UUUU, parallel, 4+0, 2(-P-P-P)

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

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List of 4 G-tetrads

 1 glyco-bond=---- sugar=-333 groove=---- planarity=0.300 type=other  O+ nts=4 GGGG 1:A.G12,1:A.G15,1:A.G22,1:A.G25
 2 glyco-bond=---- sugar=-3-3 groove=---- planarity=0.117 type=planar O+ nts=4 GGGG 1:A.G13,1:A.G16,1:A.G23,1:A.G26
 3 glyco-bond=---- sugar=-333 groove=---- planarity=0.300 type=other  O+ nts=4 GGGG 2:A.G12,2:A.G15,2:A.G22,2:A.G25
 4 glyco-bond=---- sugar=-3-3 groove=---- planarity=0.117 type=planar O+ nts=4 GGGG 2:A.G13,2:A.G16,2:A.G23,2:A.G26

List of 2 G4-helices

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, 2 G-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=---- sugar=-333 groove=---- WC-->Major O+ nts=4 GGGG 1:A.G12,1:A.G15,1:A.G22,1:A.G25
 2  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major O+ nts=4 GGGG 1:A.G13,1:A.G16,1:A.G23,1:A.G26
  step#1  pm(>>,forward)  area=10.53 rise=3.20 twist=33.9
  strand#1 RNA glyco-bond=-- sugar=-- nts=2 GG 1:A.G12,1:A.G13
  strand#2 RNA glyco-bond=-- sugar=33 nts=2 GG 1:A.G15,1:A.G16
  strand#3 RNA glyco-bond=-- sugar=3- nts=2 GG 1:A.G22,1:A.G23
  strand#4 RNA glyco-bond=-- sugar=33 nts=2 GG 1:A.G25,1:A.G26

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1 stacking diagram 
 1  glyco-bond=---- sugar=-333 groove=---- WC-->Major O+ nts=4 GGGG 1:A.G12,1:A.G15,1:A.G22,1:A.G25
 2  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major O+ nts=4 GGGG 1:A.G13,1:A.G16,1:A.G23,1:A.G26
  step#1  pm(>>,forward)  area=10.53 rise=3.20 twist=33.9

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Helix#2, 2 G-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=---- sugar=-333 groove=---- WC-->Major O+ nts=4 GGGG 2:A.G12,2:A.G15,2:A.G22,2:A.G25
 2  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major O+ nts=4 GGGG 2:A.G13,2:A.G16,2:A.G23,2:A.G26
  step#1  pm(>>,forward)  area=10.53 rise=3.20 twist=33.9
  strand#1 RNA glyco-bond=-- sugar=-- nts=2 GG 2:A.G12,2:A.G13
  strand#2 RNA glyco-bond=-- sugar=33 nts=2 GG 2:A.G15,2:A.G16
  strand#3 RNA glyco-bond=-- sugar=3- nts=2 GG 2:A.G22,2:A.G23
  strand#4 RNA glyco-bond=-- sugar=33 nts=2 GG 2:A.G25,2:A.G26

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1 stacking diagram 
 1  glyco-bond=---- sugar=-333 groove=---- WC-->Major O+ nts=4 GGGG 2:A.G12,2:A.G15,2:A.G22,2:A.G25
 2  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major O+ nts=4 GGGG 2:A.G13,2:A.G16,2:A.G23,2:A.G26
  step#1  pm(>>,forward)  area=10.53 rise=3.20 twist=33.9

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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=-333 groove=---- WC-->Major O+ nts=4 GGGG 1:A.G12,1:A.G15,1:A.G22,1:A.G25
 2  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major O+ nts=4 GGGG 1:A.G13,1:A.G16,1:A.G23,1:A.G26
  step#1  pm(>>,forward)  area=10.53 rise=3.20 twist=33.9
  strand#1  U RNA glyco-bond=-- sugar=-- nts=2 GG 1:A.G12,1:A.G13
  strand#2  U RNA glyco-bond=-- sugar=33 nts=2 GG 1:A.G15,1:A.G16
  strand#3  U RNA glyco-bond=-- sugar=3- nts=2 GG 1:A.G22,1:A.G23
  strand#4  U RNA glyco-bond=-- sugar=33 nts=2 GG 1:A.G25,1:A.G26
  loop#1 type=propeller strands=[#1,#2] nts=1 A 1:A.A14
  loop#2 type=propeller strands=[#2,#3] nts=5 UCUGA 1:A.U17,1:A.C18,1:A.U19,1:A.G20,1:A.A21
  loop#3 type=propeller strands=[#3,#4] nts=1 A 1:A.A24

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Stem#2, 2 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 2(-P-P-P)
 1  glyco-bond=---- sugar=-333 groove=---- WC-->Major O+ nts=4 GGGG 2:A.G12,2:A.G15,2:A.G22,2:A.G25
 2  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major O+ nts=4 GGGG 2:A.G13,2:A.G16,2:A.G23,2:A.G26
  step#1  pm(>>,forward)  area=10.53 rise=3.20 twist=33.9
  strand#1  U RNA glyco-bond=-- sugar=-- nts=2 GG 2:A.G12,2:A.G13
  strand#2  U RNA glyco-bond=-- sugar=33 nts=2 GG 2:A.G15,2:A.G16
  strand#3  U RNA glyco-bond=-- sugar=3- nts=2 GG 2:A.G22,2:A.G23
  strand#4  U RNA glyco-bond=-- sugar=33 nts=2 GG 2:A.G25,2:A.G26
  loop#1 type=propeller strands=[#1,#2] nts=1 A 2:A.A14
  loop#2 type=propeller strands=[#2,#3] nts=5 UCUGA 2:A.U17,2:A.C18,2:A.U19,2:A.G20,2:A.A21
  loop#3 type=propeller strands=[#3,#4] nts=1 A 2:A.A24

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