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

PDB-id
5vhe
Class
hydrolase
Method
X-ray (3.79 Å)
Summary
Dhx36 in complex with the c-myc G-quadruplex
Reference
Chen, M.C., Tippana, R., Demeshkina, N.A., Murat, P., Balasubramanian, S., Myong, S., Ferre-D'Amare, A.R.: (2018) "Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36." Nature, 558, 465-469.
Abstract
Guanine-rich nucleic acid sequences challenge the replication, transcription, and translation machinery by spontaneously folding into G-quadruplexes, the unfolding of which requires forces greater than most polymerases can exert1,2. Eukaryotic cells contain numerous helicases that can unfold G-quadruplexes 3 . The molecular basis of the recognition and unfolding of G-quadruplexes by helicases remains poorly understood. DHX36 (also known as RHAU and G4R1), a member of the DEAH/RHA family of helicases, binds both DNA and RNA G-quadruplexes with extremely high affinity4-6, is consistently found bound to G-quadruplexes in cells7,8, and is a major source of G-quadruplex unfolding activity in HeLa cell lysates 6 . DHX36 is a multi-functional helicase that has been implicated in G-quadruplex-mediated transcriptional and post-transcriptional regulation, and is essential for heart development, haematopoiesis, and embryogenesis in mice9-12. Here we report the co-crystal structure of bovine DHX36 bound to a DNA with a G-quadruplex and a 3' single-stranded DNA segment. We show that the N-terminal DHX36-specific motif folds into a DNA-binding-induced α-helix that, together with the OB-fold-like subdomain, selectively binds parallel G-quadruplexes. Comparison with unliganded and ATP-analogue-bound DHX36 structures, together with single-molecule fluorescence resonance energy transfer (FRET) analysis, suggests that G-quadruplex binding alone induces rearrangements of the helicase core; by pulling on the single-stranded DNA tail, these rearrangements drive G-quadruplex unfolding one residue at a time.
G4 notes
2 G-tetrads, 1 G4 helix, 1 G4 stem · 2(-P-P-P), parallel(4+0), UUUU

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

PyMOL session file PDB file View in 3Dmol.js

List of 2 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=---- groove=---- planarity=0.219 type=other  nts=4 GGGG B.DG3,B.DG7,B.DG11,B.DG15
 2 glyco-bond=---- groove=---- planarity=0.223 type=other  nts=4 GGGG B.DG4,B.DG8,B.DG12,B.DG16

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

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG7,B.DG11,B.DG15
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG4,B.DG8,B.DG12,B.DG16
  step#1  pm(>>,forward)  area=12.35 rise=3.36 twist=28.7
  strand#1 DNA glyco-bond=-- nts=2 GG B.DG3,B.DG4
  strand#2 DNA glyco-bond=-- nts=2 GG B.DG7,B.DG8
  strand#3 DNA glyco-bond=-- nts=2 GG B.DG11,B.DG12
  strand#4 DNA glyco-bond=-- nts=2 GG B.DG15,B.DG16

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1 stacking diagram
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG7,B.DG11,B.DG15
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG4,B.DG8,B.DG12,B.DG16
step#1 pm(>>,forward) area=12.35 rise=3.36 twist=28.7

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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, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG7,B.DG11,B.DG15
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG B.DG4,B.DG8,B.DG12,B.DG16
  step#1  pm(>>,forward)  area=12.35 rise=3.36 twist=28.7
  strand#1  U DNA glyco-bond=-- nts=2 GG B.DG3,B.DG4
  strand#2  U DNA glyco-bond=-- nts=2 GG B.DG7,B.DG8
  strand#3  U DNA glyco-bond=-- nts=2 GG B.DG11,B.DG12
  strand#4  U DNA glyco-bond=-- nts=2 GG B.DG15,B.DG16
  loop#1 type=propeller strands=[#1,#2] nts=2 TG B.DT5,B.DG6
  loop#2 type=propeller strands=[#2,#3] nts=2 TA B.DT9,B.DA10
  loop#3 type=propeller strands=[#3,#4] nts=2 GT B.DG13,B.DT14

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

List of 0 non-stem G4-loops (including the two closing Gs)