6HYU

Crystal structure of DHX8 helicase bound to single stranded poly-adenine RNA

Summary for 6HYU

• Entry DOI: 10.2210/pdb6hyu/pdb
• Descriptor: ATP-dependent RNA helicase DHX8, RNA (5'-R(*AP*AP*AP*AP*AP*A)-3'), RNA (5'-R(*A*AP*A)-3'), ... (5 entities in total)
• Functional Keywords: helicase, splicing, rna, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 156580.13

Authors

Felisberto-Rodrigues, C.,Thomas, J.C.,McAndrew, P.C.,Le Bihan, Y.V.,Burke, R.,Workman, P.,van Montfort, R.L.M. (deposition date: 2018-10-22, release date: 2019-08-28, Last modification date: 2024-05-15)

Primary citation

Felisberto-Rodrigues, C.,Thomas, J.C.,McAndrew, C.,Le Bihan, Y.V.,Burke, R.,Workman, P.,van Montfort, R.L.M.
Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release.
Biochem.J., 476:2521-2543, 2019

PubMed Abstract: DHX8 is a crucial DEAH-box RNA helicase involved in splicing and required for the release of mature mRNA from the spliceosome. Here, we report the biochemical characterisation of full-length human DHX8 and the catalytically active helicase core DHX8Δ547, alongside crystal structures of DHX8Δ547 bound to ADP and a structure of DHX8Δ547 bound to poly(A) single-strand RNA. Our results reveal that DHX8 has an binding preference for adenine-rich RNA and that RNA binding triggers the release of ADP through significant conformational flexibility in the conserved DEAH-, P-loop and hook-turn motifs. We demonstrate the importance of R620 and both the hook-turn and hook-loop regions for DHX8 helicase activity and propose that the hook-turn acts as a gatekeeper to regulate the directional movement of the 3' end of RNA through the RNA-binding channel. This study provides an in-depth understanding of the activity of DHX8 and contributes insights into the RNA-unwinding mechanisms of the DEAH-box helicase family.

PubMed: 31409651
DOI: 10.1042/BCJ20190383

Experimental method

X-RAY DIFFRACTION (3.22 Å)