5vhe | pdb_00005vhe
DHX36 in complex with the c-Myc G-quadruplex
Structural highlights
Publication Abstract from PubMedGuanine-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 alpha-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. Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36.,Chen MC, Tippana R, Demeshkina NA, Murat P, Balasubramanian S, Myong S, Ferre-D'Amare AR Nature. 2018 Jun 13. pii: 10.1038/s41586-018-0209-9. doi:, 10.1038/s41586-018-0209-9. PMID:29899445[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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