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

PDB-id
5ua3
Class
DNA
Method
X-ray (1.88 Å)
Summary
Crystal structure of a DNA G-quadruplex with a cytosine bulge
Reference
Meier, M., Moya-Torres, A., Krahn, N.J., McDougall, M.D., Orriss, G.L., McRae, E.K.S., Booy, E.P., McEleney, K., Patel, T.R., McKenna, S.A., Stetefeld, J.: (2018) "Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge." Nucleic Acids Res., 46, 5319-5331.
Abstract
The identification of four-stranded G-quadruplexes (G4s) has highlighted the fact that DNA has additional spatial organisations at its disposal other than double-stranded helices. Recently, it became clear that the formation of G4s is not limited to the traditional G3+NL1G3+NL2G3+NL3G3+ sequence motif. Instead, the G3 triplets can be interrupted by deoxythymidylate (DNA) or uridylate (RNA) where the base forms a bulge that loops out from the G-quadruplex core. Here, we report the first high-resolution X-ray structure of a unique unimolecular DNA G4 with a cytosine bulge. The G4 forms a dimer that is stacked via its 5'-tetrads. Analytical ultracentrifugation, static light scattering and small angle X-ray scattering confirmed that the G4 adapts a predominantly dimeric structure in solution. We provide a comprehensive comparison of previously published G4 structures containing bulges and report a special γ torsion angle range preferentially populated by the G4 core guanylates adjacent to bulges. Since the penalty for introducing bulges appears to be negligible, it should be possible to functionalize G4s by introducing artificial or modified nucleotides at such positions. The presence of the bulge alters the surface of the DNA, providing an opportunity to develop drugs that can specifically target individual G4s.
G4 notes
6 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack · 3(-P-P-P), parallel(4+0), UUUU · coaxial interfaces: 5'/5'

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

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List of 6 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=---- groove=---- planarity=0.097 type=planar nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15
 2 glyco-bond=---- groove=---- planarity=0.195 type=bowl-2 nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16
 3 glyco-bond=---- groove=---- planarity=0.229 type=bowl   nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG17
 4 glyco-bond=---- groove=---- planarity=0.088 type=planar nts=4 GGGG B.DG1,B.DG6,B.DG11,B.DG15
 5 glyco-bond=---- groove=---- planarity=0.171 type=bowl-2 nts=4 GGGG B.DG2,B.DG8,B.DG12,B.DG16
 6 glyco-bond=---- groove=---- planarity=0.275 type=bowl   nts=4 GGGG B.DG3,B.DG9,B.DG13,B.DG17

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, 6 G-tetrad layers, inter-molecular, with 2 stems

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG17
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16
 3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15
 4  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG B.DG6,B.DG1,B.DG15,B.DG11
 5  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG B.DG8,B.DG2,B.DG16,B.DG12
 6  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG B.DG9,B.DG3,B.DG17,B.DG13
  step#1  mp(<<,backward) area=9.89  rise=3.42 twist=30.1
  step#2  mp(<<,backward) area=10.82 rise=3.35 twist=30.1
  step#3  mm(<>,outward)  area=28.50 rise=3.32 twist=-9.1
  step#4  pm(>>,forward)  area=10.39 rise=3.31 twist=31.0
  step#5  pm(>>,forward)  area=9.91  rise=3.41 twist=29.4
  strand#1 DNA glyco-bond=------ nts=6 GGGGGG A.DG3,A.DG2,A.DG1,B.DG6,B.DG8,B.DG9
  strand#2 DNA glyco-bond=------ nts=6 GGGGGG A.DG9,A.DG8,A.DG6,B.DG1,B.DG2,B.DG3
  strand#3 DNA glyco-bond=------ nts=6 GGGGGG A.DG13,A.DG12,A.DG11,B.DG15,B.DG16,B.DG17
  strand#4 DNA glyco-bond=------ nts=6 GGGGGG A.DG17,A.DG16,A.DG15,B.DG11,B.DG12,B.DG13

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5 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG17
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16
step#1 mp(<<,backward) area=9.89 rise=3.42 twist=30.1

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16
3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15
step#2 mp(<<,backward) area=10.82 rise=3.35 twist=30.1

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 3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15
4 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG B.DG6,B.DG1,B.DG15,B.DG11
step#3 mm(<>,outward) area=28.50 rise=3.32 twist=-9.1

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 4  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG B.DG6,B.DG1,B.DG15,B.DG11
5 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG B.DG8,B.DG2,B.DG16,B.DG12
step#4 pm(>>,forward) area=10.39 rise=3.31 twist=31.0

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 5  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG B.DG8,B.DG2,B.DG16,B.DG12
6 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG B.DG9,B.DG3,B.DG17,B.DG13
step#5 pm(>>,forward) area=9.91 rise=3.41 twist=29.4

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

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG17
  step#1  pm(>>,forward)  area=10.82 rise=3.35 twist=30.1
  step#2  pm(>>,forward)  area=9.89  rise=3.42 twist=30.1
  strand#1  U DNA glyco-bond=--- nts=3 GGG A.DG1,A.DG2,A.DG3
  strand#2* U DNA glyco-bond=--- nts=3 GGG A.DG6,A.DG8,A.DG9 bulged-nts=1 C A.DC7
  strand#3  U DNA glyco-bond=--- nts=3 GGG A.DG11,A.DG12,A.DG13
  strand#4  U DNA glyco-bond=--- nts=3 GGG A.DG15,A.DG16,A.DG17
  loop#1 type=propeller strands=[#1,#2] nts=2 TT A.DT4,A.DT5
  loop#2 type=propeller strands=[#2,#3] nts=1 A A.DA10
  loop#3 type=propeller strands=[#3,#4] nts=1 T A.DT14

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

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG1,B.DG6,B.DG11,B.DG15
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG2,B.DG8,B.DG12,B.DG16
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG9,B.DG13,B.DG17
  step#1  pm(>>,forward)  area=10.39 rise=3.31 twist=31.0
  step#2  pm(>>,forward)  area=9.91  rise=3.41 twist=29.4
  strand#1  U DNA glyco-bond=--- nts=3 GGG B.DG1,B.DG2,B.DG3
  strand#2* U DNA glyco-bond=--- nts=3 GGG B.DG6,B.DG8,B.DG9 bulged-nts=1 C B.DC7
  strand#3  U DNA glyco-bond=--- nts=3 GGG B.DG11,B.DG12,B.DG13
  strand#4  U DNA glyco-bond=--- nts=3 GGG B.DG15,B.DG16,B.DG17
  loop#1 type=propeller strands=[#1,#2] nts=2 TT B.DT4,B.DT5
  loop#2 type=propeller strands=[#2,#3] nts=1 A B.DA10
  loop#3 type=propeller strands=[#3,#4] nts=1 T B.DT14

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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)