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

PDB-id
6h1k
Class
DNA
Method
NMR
Summary
The major G-quadruplex form of hiv-1 ltr
Reference
Butovskaya, E., Heddi, B., Bakalar, B., Richter, S.N., Phan, A.T.: (2018) "Major G-Quadruplex Form of HIV-1 LTR Reveals a (3 + 1) Folding Topology Containing a Stem-Loop." J. Am. Chem. Soc., 140, 13654-13662.
Abstract
Nucleic acids can form noncanonical four-stranded structures called G-quadruplexes. G-quadruplex-forming sequences are found in several genomes including human and viruses. Previous studies showed that the G-rich sequence located in the U3 promoter region of the HIV-1 long terminal repeat (LTR) folds into a set of dynamically interchangeable G-quadruplex structures. G-quadruplexes formed in the LTR could act as silencer elements to regulate viral transcription. Stabilization of LTR G-quadruplexes by G-quadruplex-specific ligands resulted in decreased viral production, suggesting the possibility of targeting viral G-quadruplex structures for antiviral purposes. Among all the G-quadruplexes formed in the LTR sequence, LTR-III was shown to be the major G-quadruplex conformation in vitro. Here we report the NMR structure of LTR-III in K+ solution, revealing the formation of a unique quadruplex-duplex hybrid consisting of a three-layer (3 + 1) G-quadruplex scaffold, a 12-nt diagonal loop containing a conserved duplex-stem, a 3-nt lateral loop, a 1-nt propeller loop, and a V-shaped loop. Our structure showed several distinct features including a quadruplex-duplex junction, representing an attractive motif for drug targeting. The structure solved in this study may be used as a promising target to selectively impair the viral cycle.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · 2(D+PX), UD3(1+3), UDDD

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

PyMOL session file PDB file View in 3Dmol.js

List of 3 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=s--- groove=w--n planarity=0.149 type=planar nts=4 GGGG A.DG1,A.DG20,A.DG16,A.DG27
 2 glyco-bond=-sss groove=w--n planarity=0.136 type=planar nts=4 GGGG A.DG2,A.DG19,A.DG15,A.DG26
 3 glyco-bond=--s- groove=-wn- planarity=0.307 type=other  nts=4 GGGG A.DG17,A.DG21,A.DG25,A.DG28

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, 3 G-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=-sss groove=w--n WC-->Major nts=4 GGGG A.DG2,A.DG19,A.DG15,A.DG26
 2  glyco-bond=s--- groove=w--n Major-->WC nts=4 GGGG A.DG1,A.DG20,A.DG16,A.DG27
 3  glyco-bond=s--- groove=w--n Major-->WC nts=4 GGGG A.DG25,A.DG21,A.DG17,A.DG28
  step#1  mm(<>,outward)  area=12.76 rise=3.47 twist=18.2
  step#2  pm(>>,forward)  area=12.84 rise=3.07 twist=33.4
  strand#1 DNA glyco-bond=-ss nts=3 GGG A.DG2,A.DG1,A.DG25
  strand#2 DNA glyco-bond=s-- nts=3 GGG A.DG19,A.DG20,A.DG21
  strand#3 DNA glyco-bond=s-- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4 DNA glyco-bond=s-- nts=3 GGG A.DG26,A.DG27,A.DG28

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2 stacking diagrams
 1  glyco-bond=-sss groove=w--n WC-->Major nts=4 GGGG A.DG2,A.DG19,A.DG15,A.DG26
2 glyco-bond=s--- groove=w--n Major-->WC nts=4 GGGG A.DG1,A.DG20,A.DG16,A.DG27
step#1 mm(<>,outward) area=12.76 rise=3.47 twist=18.2

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 2  glyco-bond=s--- groove=w--n Major-->WC nts=4 GGGG A.DG1,A.DG20,A.DG16,A.DG27
3 glyco-bond=s--- groove=w--n Major-->WC nts=4 GGGG A.DG25,A.DG21,A.DG17,A.DG28
step#2 pm(>>,forward) area=12.84 rise=3.07 twist=33.4

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List of 1 G4-stem [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, 2 G-tetrad layers, 3 loops, INTRA-molecular, UDDD, hybrid-(mixed), 2(D+PX), UD3(1+3)

 1  glyco-bond=s--- groove=w--n Major-->WC nts=4 GGGG A.DG1,A.DG20,A.DG16,A.DG27
 2  glyco-bond=-sss groove=w--n WC-->Major nts=4 GGGG A.DG2,A.DG19,A.DG15,A.DG26
  step#1  mm(<>,outward)  area=12.76 rise=3.47 twist=18.2
  strand#1  U DNA glyco-bond=s- nts=2 GG A.DG1,A.DG2
  strand#2  D DNA glyco-bond=-s nts=2 GG A.DG20,A.DG19
  strand#3  D DNA glyco-bond=-s nts=2 GG A.DG16,A.DG15
  strand#4  D DNA glyco-bond=-s nts=2 GG A.DG27,A.DG26
  loop#1 type=diagonal  strands=[#1,#3] nts=12 GAGGCGTGGCCT A.DG3,A.DA4,A.DG5,A.DG6,A.DC7,A.DG8,A.DT9,A.DG10,A.DG11,A.DC12,A.DC13,A.DT14
  loop#2 type=propeller strands=[#3,#2] nts=2 GC A.DG17,A.DC18
  loop#3 type=diag-prop strands=[#2,#4] nts=5 GACTG A.DG21,A.DA22,A.DC23,A.DT24,A.DG25

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List of 0 G4 coaxial stacks [summary · schematics · tetrads · helices · stems · homepage]

List of 2 non-stem G4-loops (including the two closing Gs)

 1 type=lateral   helix=#1 nts=5 GACTG A.DG21,A.DA22,A.DC23,A.DT24,A.DG25
 2 type=V-shaped  helix=#1 nts=4 GGGG A.DG25,A.DG26,A.DG27,A.DG28