DSSR-derived G-quadruplex features in PDB entry 2mb4
- Solution structure of a stacked dimeric G-quadruplex formed by a segment of the human ceb1 minisatellite
- Adrian, M., Ang, D.J., Lech, C.J., Heddi, B., Nicolas, A., Phan, A.T.: (2014) "Structure and Conformational Dynamics of a Stacked Dimeric G-Quadruplex Formed by the Human CEB1 Minisatellite." J.Am.Chem.Soc., 136, 6297-6305.
- CEB1 is a highly polymorphic human minisatellite. In yeast, the size variation of CEB1 tandem arrays has been associated with the capacity of the motif to form G-quadruplexes. Here we report on the NMR solution structure of a G-quadruplex formed by the CEB1 DNA G-rich fragment d(AGGGGGGAGGGAGGGTGG), harboring several G-tracts including one with six continuous guanines. This sequence forms a dimeric G-quadruplex involving the stacking of two subunits, each being a unique snapback parallel-stranded scaffold with three G-tetrad layers, three double-chain-reversal loops, and a V-shaped loop. The two subunits are stacked at their 5'-end tetrads, and multiple stacking rotamers may be present due to a high symmetry at the stacking interface. There is a conformational exchange in the millisecond time scale involving a swapping motion between two bases of the six-guanine tract. Our results not only add to the understanding of how the G-quadruplex formation in human minisatellite leads to genetic instability but also address the fundamental questions regarding stacking of G-quadruplexes and how a long continuous G-tract participates in the structure and conformational dynamics of G-quadruplexes.
- G4 notes
- 6 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack · 2(-P-P-P), parallel(4+0), UUUU · coaxial interfaces: 5'/5'
1 glyco-bond=s--- groove=w--n planarity=0.198 type=other nts=4 GGGG A.DG3,A.DG15,A.DG11,A.DG7 2 glyco-bond=---- groove=---- planarity=0.106 type=planar nts=4 GGGG A.DG5,A.DG9,A.DG13,A.DG17 3 glyco-bond=---- groove=---- planarity=0.141 type=planar nts=4 GGGG A.DG6,A.DG10,A.DG14,A.DG18 4 glyco-bond=s--- groove=w--n planarity=0.163 type=other nts=4 GGGG B.DG3,B.DG15,B.DG11,B.DG7 5 glyco-bond=---- groove=---- planarity=0.155 type=planar nts=4 GGGG B.DG5,B.DG9,B.DG13,B.DG17 6 glyco-bond=---- groove=---- planarity=0.143 type=planar nts=4 GGGG B.DG6,B.DG10,B.DG14,B.DG18
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
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-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)
Stem#2, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)
1 G4 helix#1 contains 2 G4 stems: [#1,#2] [5'/5']
List of 2 non-stem G4-loops (including the two closing Gs)
1 type=V-shaped helix=#1 nts=5 GGGGG A.DG3,A.DG4,A.DG5,A.DG6,A.DG7 2 type=V-shaped helix=#1 nts=5 GGGGG B.DG3,B.DG4,B.DG5,B.DG6,B.DG7