DSSR-enabled G4 identification/annotation: PDB entry 8dut
Summary information and primary citation
- PDB-id
- 8dut
- Class
- DNA
- Method
- cryo-EM (7.4 Å)
- Summary
- Duplex-g-quadruplex-duplex (dgd) class_1
- Reference
- Monsen RC, Chua EYD, Hopkins JB, Chaires JB, Trent JO (2023): "Structure of a 28.5 kDa duplex-embedded G-quadruplex system resolved to 7.4 angstrom resolution with cryo-EM." Nucleic Acids Res., 51, 1943-1959. doi: 10.1093/nar/gkad014.
- Abstract
- Genomic regions with high guanine content can fold into non-B form DNA four-stranded structures known as G-quadruplexes (G4s). Extensive in vivo investigations have revealed that promoter G4s are transcriptional regulators. Little structural information exists for these G4s embedded within duplexes, their presumed genomic environment. Here, we report the 7.4 Å resolution structure and dynamics of a 28.5 kDa duplex-G4-duplex (DGD) model system using cryo-EM, molecular dynamics, and small-angle X-ray scattering (SAXS) studies. The DGD cryo-EM refined model features a 53° bend induced by a stacked duplex-G4 interaction at the 5' G-tetrad interface with a persistently unstacked 3' duplex. The surrogate complement poly dT loop preferably stacks onto the 3' G-tetrad interface resulting in occlusion of both 5' and 3' tetrad interfaces. Structural analysis shows that the DGD model is quantifiably more druggable than the monomeric G4 structure alone and represents a new structural drug target. Our results illustrate how the integration of cryo-EM, MD, and SAXS can reveal complementary detailed static and dynamic structural information on DNA G4 systems.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 3(-P-P-P)
Cartoon-block schematics in six views (download the tarball)
List of 3 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.426 type=other O+ nts=4 GGGG B.DG62,B.DG66,B.DG71,B.DG75 2 glyco-bond=---- sugar=---- groove=---- planarity=0.451 type=other O+ nts=4 GGGG B.DG63,B.DG67,B.DG72,B.DG76 3 glyco-bond=---- sugar=---- groove=---- planarity=0.421 type=bowl O+ nts=4 GGGG B.DG64,B.DG68,B.DG73,B.DG77
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=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG62,B.DG66,B.DG71,B.DG75 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG63,B.DG67,B.DG72,B.DG76 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG64,B.DG68,B.DG73,B.DG77 step#1 pm(>>,forward) area=21.23 rise=3.68 twist=20.9 step#2 pm(>>,forward) area=13.20 rise=3.49 twist=25.3 strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG62,B.DG63,B.DG64 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG66,B.DG67,B.DG68 strand#3 DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG71,B.DG72,B.DG73 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG75,B.DG76,B.DG77 |
| 2 stacking diagrams | |
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG62,B.DG66,B.DG71,B.DG75 |
|
2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG63,B.DG67,B.DG72,B.DG76 |
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, UUUU, parallel, 4+0, 3(-P-P-P)
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG62,B.DG66,B.DG71,B.DG75 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG63,B.DG67,B.DG72,B.DG76 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG64,B.DG68,B.DG73,B.DG77 step#1 pm(>>,forward) area=21.23 rise=3.68 twist=20.9 step#2 pm(>>,forward) area=13.20 rise=3.49 twist=25.3 strand#1 U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG62,B.DG63,B.DG64 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG66,B.DG67,B.DG68 strand#3 U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG71,B.DG72,B.DG73 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG75,B.DG76,B.DG77 loop#1 type=propeller strands=[#1,#2] nts=1 T B.DT65 loop#2 type=propeller strands=[#2,#3] nts=2 TA B.DT69,B.DA70 loop#3 type=propeller strands=[#3,#4] nts=1 T B.DT74 |