The structure of Prp2 bound to RNA and ADP-BeF 3 − reveals structural features important for RNA unwinding by DEAH-box ATPases
2021 | journal article; research paper. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
The structure of Prp2 bound to RNA and ADP-BeF 3 − reveals structural features important for RNA unwinding by DEAH-box ATPases
Hamann, F.; Zimmerningkat, L. C.; Becker, R. A.; Garbers, T. B.; Neumann, P.; Hub, J. S. & Ficner, R. (2021)
Acta Crystallographica Section D Structural Biology, 77(4) pp. 496-509. DOI: https://doi.org/10.1107/S2059798321001194
Documents & Media
License
Details
- Authors
- Hamann, Florian; Zimmerningkat, Lars C.; Becker, Robert A.; Garbers, Tim B.; Neumann, Piotr; Hub, Jochen S.; Ficner, Ralf
- Abstract
- Noncoding intron sequences present in precursor mRNAs need to be removed prior to translation, and they are excised via the spliceosome, a multimegadalton molecular machine composed of numerous protein and RNA components. The DEAH-box ATPase Prp2 plays a crucial role during pre-mRNA splicing as it ensures the catalytic activation of the spliceosome. Despite high structural similarity to other spliceosomal DEAH-box helicases, Prp2 does not seem to function as an RNA helicase, but rather as an RNA-dependent ribonucleoprotein particle-modifying ATPase. Recent crystal structures of the spliceosomal DEAH-box ATPases Prp43 and Prp22, as well as of the related RNA helicase MLE, in complex with RNA have contributed to a better understanding of how RNA binding and processivity might be achieved in this helicase family. In order to shed light onto the divergent manner of function of Prp2, an N-terminally truncated construct of Chaetomium thermophilum Prp2 was crystallized in the presence of ADP-BeF 3 − and a poly-U 12 RNA. The refined structure revealed a virtually identical conformation of the helicase core compared with the ADP-BeF 3 − - and RNA-bound structure of Prp43, and only a minor shift of the C-terminal domains. However, Prp2 and Prp43 differ in the hook-loop and a loop of the helix-bundle domain, which interacts with the hook-loop and evokes a different RNA conformation immediately after the 3′ stack. On replacing these loop residues in Prp43 by the Prp2 sequence, the unwinding activity of Prp43 was abolished. Furthermore, a putative exit tunnel for the γ-phosphate after ATP hydrolysis could be identified in one of the Prp2 structures.
- Issue Date
- 2021
- Publisher
- International Union of Crystallography
- Journal
- Acta Crystallographica Section D Structural Biology
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Ficner (Molecular Structural Biology)
- ISSN
- 2059-7983
- Language
- English