5VHC

DHX36 with an N-terminal truncation bound to ADP-BeF3

Summary for 5VHC

• Entry DOI: 10.2210/pdb5vhc/pdb
• Related: 5VHA 5VHD 5VHE
• Descriptor: DEAH (Asp-Glu-Ala-His) box polypeptide 36, MAGNESIUM ION, BERYLLIUM TRIFLUORIDE ION, ... (5 entities in total)
• Functional Keywords: hydrolase
• Biological source: Bos taurus (Bovine)
• Total number of polymer chains: 1
• Total formula weight: 100728.85

Authors

Chen, M.,Ferre-D'Amare, A. (deposition date: 2017-04-12, release date: 2018-06-13, Last modification date: 2024-04-03)

Primary citation

Chen, M.C.,Tippana, R.,Demeshkina, N.A.,Murat, P.,Balasubramanian, S.,Myong, S.,Ferre-D'Amare, A.R.
Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36.
Nature, 558:465-469, 2018

PubMed 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 exert. Eukaryotic cells contain numerous helicases that can unfold G-quadruplexes . 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, is consistently found bound to G-quadruplexes in cells, and is a major source of G-quadruplex unfolding activity in HeLa cell lysates . 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. 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.

PubMed: 29899445
DOI: 10.1038/s41586-018-0209-9

Experimental method

X-RAY DIFFRACTION (2.49 Å)