TY - JOUR
AU - Ferré-D’Amaré, Adrian
AB - 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 exert
1,2
. 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 affinity
4–6
, is consistently found bound to G-quadruplexes in cells
7,8
, 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 mice
9–12
. 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.
TI - Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36
JF - Nature
DO - 10.1038/s41586-018-0209-9
DA - 2018-06-13
UR - https://www.deepdyve.com/lp/springer-journals/structural-basis-of-g-quadruplex-unfolding-by-the-deah-rha-helicase-cP1sxDHCPS
SP - 465
EP - 469
VL - 558
IS - 7710
DP - DeepDyve
ER -