Summary information and primary citation

PDB-id
2f8u
Class
DNA
Method
NMR
Summary
G-quadruplex structure formed in human bcl-2 promoter, hybrid form
Reference
Dai J, Chen D, Jones RA, Hurley LH, Yang D (2006): "NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region." Nucleic Acids Res., 34, 5133-5144. doi: 10.1093/nar/gkl610.
Abstract
BCL2 protein functions as an inhibitor of cell apoptosis and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the P1 promoter plays an important role in the transcriptional regulation of BCL2. Here we report the NMR solution structure of the major intramolecular G-quadruplex formed on the G-rich strand of this region in K+ solution. This well-defined mixed parallel/antiparallel-stranded G-quadruplex structure contains three G-tetrads of mixed G-arrangements, which are connected with two lateral loops and one side loop, and four grooves of different widths. The three loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure. The loop conformations are in accord with the experimental mutation and footprinting data. The first 3-nt loop adopts a lateral loop conformation and appears to determine the overall folding of the BCL2 G-quadruplex. The third 1-nt double-chain-reversal loop defines another example of a stable parallel-stranded structural motif using the G3NG3 sequence. Significantly, the distinct major BCL2 promoter G-quadruplex structure suggests that it can be specifically involved in gene modulation and can be an attractive target for pathway-specific drug design.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UDUU, hybrid3, 3+1, 3(-Lw-Ln-P)

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

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List of 3 G-tetrads

 1 glyco-bond=s-ss sugar=..-. groove=wn-- planarity=0.176 type=other  O- nts=4 GGGG A.DG1,A.DG9,A.DG17,A.DG21
 2 glyco-bond=-s-- sugar=..-- groove=wn-- planarity=0.172 type=other  O+ nts=4 GGGG A.DG2,A.DG8,A.DG18,A.DG22
 3 glyco-bond=-s-- sugar=.-.. groove=wn-- planarity=0.284 type=other  O+ nts=4 GGGG A.DG3,A.DG7,A.DG19,A.DG23

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-ss sugar=..-. groove=wn-- Major-->WC O- nts=4 GGGG A.DG1,A.DG9,A.DG17,A.DG21
 2  glyco-bond=-s-- sugar=..-- groove=wn-- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG18,A.DG22
 3  glyco-bond=-s-- sugar=.-.. groove=wn-- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG19,A.DG23
  step#1  mm(<>,outward)  area=12.90 rise=3.92 twist=20.6
  step#2  pm(>>,forward)  area=14.70 rise=3.11 twist=28.2
  strand#1 DNA glyco-bond=s-- sugar=... nts=3 GGG A.DG1,A.DG2,A.DG3
  strand#2 DNA glyco-bond=-ss sugar=..- nts=3 GGG A.DG9,A.DG8,A.DG7
  strand#3 DNA glyco-bond=s-- sugar=--. nts=3 GGG A.DG17,A.DG18,A.DG19
  strand#4 DNA glyco-bond=s-- sugar=.-. nts=3 GGG A.DG21,A.DG22,A.DG23

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2 stacking diagrams 
 1  glyco-bond=s-ss sugar=..-. groove=wn-- Major-->WC O- nts=4 GGGG A.DG1,A.DG9,A.DG17,A.DG21
 2  glyco-bond=-s-- sugar=..-- groove=wn-- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG18,A.DG22
  step#1  mm(<>,outward)  area=12.90 rise=3.92 twist=20.6

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 2  glyco-bond=-s-- sugar=..-- groove=wn-- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG18,A.DG22
 3  glyco-bond=-s-- sugar=.-.. groove=wn-- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG19,A.DG23
  step#2  pm(>>,forward)  area=14.70 rise=3.11 twist=28.2

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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, UDUU, hybrid3, 3+1, 3(-Lw-Ln-P)
 1  glyco-bond=s-ss sugar=..-. groove=wn-- Major-->WC O- nts=4 GGGG A.DG1,A.DG9,A.DG17,A.DG21
 2  glyco-bond=-s-- sugar=..-- groove=wn-- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG18,A.DG22
 3  glyco-bond=-s-- sugar=.-.. groove=wn-- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG19,A.DG23
  step#1  mm(<>,outward)  area=12.90 rise=3.92 twist=20.6
  step#2  pm(>>,forward)  area=14.70 rise=3.11 twist=28.2
  strand#1  U DNA glyco-bond=s-- sugar=... nts=3 GGG A.DG1,A.DG2,A.DG3
  strand#2  D DNA glyco-bond=-ss sugar=..- nts=3 GGG A.DG9,A.DG8,A.DG7
  strand#3  U DNA glyco-bond=s-- sugar=--. nts=3 GGG A.DG17,A.DG18,A.DG19
  strand#4  U DNA glyco-bond=s-- sugar=.-. nts=3 GGG A.DG21,A.DG22,A.DG23
  loop#1 type=lateral   strands=[#1,#2] nts=3 CGC A.DC4,A.DG5,A.DC6
  loop#2 type=lateral   strands=[#2,#3] nts=7 AGGAATT A.DA10,A.DG11,A.DG12,A.DA13,A.DA14,A.DT15,A.DT16
  loop#3 type=propeller strands=[#3,#4] nts=1 C A.DC20

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