Summary information and primary citation

PDB-id
5yey
Class
DNA
Method
NMR
Summary
The structure of a chair-type g-quadruplex of the human telomeric variant in k+ solution
Reference
Liu C, Zhou B, Geng Y, Yan Tam D, Feng R, Miao H, Xu N, Shi X, You Y, Hong Y, Tang BZ, Kwan Lo P, Kuryavyi V, Zhu G (2019): "A chair-type G-quadruplex structure formed by a human telomeric variant DNA in K+solution." Chem Sci, 10, 218-226. doi: 10.1039/c8sc03813a.
Abstract
Guanine tracts of human telomeric DNA sequences are known to fold into eight different four-stranded structures that vary by the conformation of guanine nucleotides arranged in the stack of G-tetrads in their core and by different kinds and orders of connecting loops, called G-quadruplexes. Here, we present a novel G-quadruplex structure formed in K<sub>+</sub> solution by a human telomeric variant d[(GGGTTA)2GGGTTTGGG], <i>htel21</i>T<sub>18</sub>. This variant DNA is located in the subtelomeric regions of human chromosomes 8, 11, 17, and 19 as well as in the DNase hypersensitive region and in the subcentromeric region of chromosome 5. Interestingly, single A18T substitution that makes <i>htel21</i>T<sub>18</sub> different from the human telomeric sequence results in the formation of a three-layer chair-type G-quadruplex, a fold previously unknown among human telomeric repeats, with two loops interacting through the reverse Watson-Crick A6·T18 base pair. The loops are edgewise; glycosidic conformation of guanines is <i>syn</i>·<i>anti</i>·<i>syn</i>·<i>anti</i> around each tetrad, and each strand of the core has two antiparallel adjacent strands. Our results expand the repertoire of known G-quadruplex folding topologies and may provide a potential target for structure-based anticancer drug design.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UDUD, anti-parallel:chair, 2+2, 3(+Ln+Lw+Ln)

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List of 3 G-tetrads

 1 glyco-bond=s-s- sugar=-.-- groove=wnwn planarity=0.080 type=planar O+ nts=4 GGGG A.DG1,A.DG21,A.DG13,A.DG9
 2 glyco-bond=-s-s sugar=---3 groove=wnwn planarity=0.010 type=planar O- nts=4 GGGG A.DG2,A.DG20,A.DG14,A.DG8
 3 glyco-bond=-s-s sugar=3--- groove=wnwn planarity=0.063 type=planar O- nts=4 GGGG A.DG3,A.DG19,A.DG15,A.DG7

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, 3 G-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=s-s- sugar=-.-- groove=wnwn Major-->WC O+ nts=4 GGGG A.DG1,A.DG21,A.DG13,A.DG9
 2  glyco-bond=-s-s sugar=---3 groove=wnwn WC-->Major O- nts=4 GGGG A.DG2,A.DG20,A.DG14,A.DG8
 3  glyco-bond=-s-s sugar=3--- groove=wnwn WC-->Major O- nts=4 GGGG A.DG3,A.DG19,A.DG15,A.DG7
  step#1  mm(<>,outward)  area=12.07 rise=3.46 twist=18.4
  step#2  pm(>>,forward)  area=9.90  rise=3.34 twist=32.3
  strand#1 DNA glyco-bond=s-- sugar=--3 nts=3 GGG A.DG1,A.DG2,A.DG3
  strand#2 DNA glyco-bond=-ss sugar=.-- nts=3 GGG A.DG21,A.DG20,A.DG19
  strand#3 DNA glyco-bond=s-- sugar=--- nts=3 GGG A.DG13,A.DG14,A.DG15
  strand#4 DNA glyco-bond=-ss sugar=-3- nts=3 GGG A.DG9,A.DG8,A.DG7

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2 stacking diagrams 
 1  glyco-bond=s-s- sugar=-.-- groove=wnwn Major-->WC O+ nts=4 GGGG A.DG1,A.DG21,A.DG13,A.DG9
 2  glyco-bond=-s-s sugar=---3 groove=wnwn WC-->Major O- nts=4 GGGG A.DG2,A.DG20,A.DG14,A.DG8
  step#1  mm(<>,outward)  area=12.07 rise=3.46 twist=18.4

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 2  glyco-bond=-s-s sugar=---3 groove=wnwn WC-->Major O- nts=4 GGGG A.DG2,A.DG20,A.DG14,A.DG8
 3  glyco-bond=-s-s sugar=3--- groove=wnwn WC-->Major O- nts=4 GGGG A.DG3,A.DG19,A.DG15,A.DG7
  step#2  pm(>>,forward)  area=9.90  rise=3.34 twist=32.3

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List of 1 G4-stem

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-tetrads, 3 loops, INTRA-molecular, UDUD, anti-parallel:chair, 2+2, 3(+Ln+Lw+Ln)
 1  glyco-bond=s-s- sugar=-.-- groove=wnwn Major-->WC O+ nts=4 GGGG A.DG1,A.DG21,A.DG13,A.DG9
 2  glyco-bond=-s-s sugar=---3 groove=wnwn WC-->Major O- nts=4 GGGG A.DG2,A.DG20,A.DG14,A.DG8
 3  glyco-bond=-s-s sugar=3--- groove=wnwn WC-->Major O- nts=4 GGGG A.DG3,A.DG19,A.DG15,A.DG7
  step#1  mm(<>,outward)  area=12.07 rise=3.46 twist=18.4
  step#2  pm(>>,forward)  area=9.90  rise=3.34 twist=32.3
  strand#1  U DNA glyco-bond=s-- sugar=--3 nts=3 GGG A.DG1,A.DG2,A.DG3
  strand#2  D DNA glyco-bond=-ss sugar=.-- nts=3 GGG A.DG21,A.DG20,A.DG19
  strand#3  U DNA glyco-bond=s-- sugar=--- nts=3 GGG A.DG13,A.DG14,A.DG15
  strand#4  D DNA glyco-bond=-ss sugar=-3- nts=3 GGG A.DG9,A.DG8,A.DG7
  loop#1 type=lateral   strands=[#1,#4] nts=3 TTA A.DT4,A.DT5,A.DA6
  loop#2 type=lateral   strands=[#4,#3] nts=3 TTA A.DT10,A.DT11,A.DA12
  loop#3 type=lateral   strands=[#3,#2] nts=3 TTT A.DT16,A.DT17,A.DT18

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