6ZM2

Crystal structure of the DEAH-box ATPase Prp2 in complex with ADP-BeF3 and ssRNA

Summary for 6ZM2

• Entry DOI: 10.2210/pdb6zm2/pdb
• Descriptor: Putative mRNA splicing factor, S-1,2-PROPANEDIOL, HEXANE-1,6-DIOL, ... (14 entities in total)
• Functional Keywords: prp2, deah-box, spliceosome, rna, hydrolase
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719); More
• Total number of polymer chains: 2
• Total formula weight: 75724.99

Authors

Hamann, F.,Ficner, R. (deposition date: 2020-07-01, release date: 2021-04-21, Last modification date: 2024-01-31)

Primary citation

Hamann, F.,Zimmerningkat, L.C.,Becker, R.A.,Garbers, T.B.,Neumann, P.,Hub, J.S.,Ficner, R.
The structure of Prp2 bound to RNA and ADP-BeF 3 - reveals structural features important for RNA unwinding by DEAH-box ATPases.
Acta Crystallogr D Struct Biol, 77:496-509, 2021

PubMed 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 and a poly-U RNA. The refined structure revealed a virtually identical conformation of the helicase core compared with the ADP-BeF- 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.

PubMed: 33825710
DOI: 10.1107/S2059798321001194

Experimental method

X-RAY DIFFRACTION (2.1 Å)