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.

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​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 Biology77(4) pp. 496​-509​.​ DOI: https://doi.org/10.1107/S2059798321001194 

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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

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