Journal:Acta Cryst D:S2059798322009755

Structural and functional investigation of the human snRNP assembly factor AAR2 in complex with the PRPF8 RNaseH domain

Marco Preussner, Karine F. Santos, Jonathan Alles, Christina Heroven, Florian Heyd, Markus C. Wahl, Gert Weber ^[1]

Molecular Tour
Most of the metazoan genes are interspersed with non-coding information, so called introns. A large macromolecular machinery in the nucleus, the spliceosome, removes these introns from pre-mRNA transcripts linking the coding exons, to yield functional genes for translation.

. In this and the following scenes: AAR2^Δloop, orange; PRPF8^RH, light blue; a flexible loop (labeled Ser3) of AAR2 connecting its two domains, which in AAR2^Δloop was replaced by three serine residues and another smaller flexible loop between residues 313-321 are labeled. N- and C-termini as well as the β-finger module of PRPF8^RH are labeled.

in complex with human AAR2^Δloop and yeast Aar2p/PRPF8^JM (PDB ID 4i43) respectively, to illustrate the human AAR2 in a larger PRPF8 context. In this and the following scenes: Aar2p, maroon; Prp8p^RH, dark blue; Prp8p^JM, cyan.

(PDB ID 4ilg).

. Water molecules are shown as red spheres. Interacting residues are shown as ball-and-sticks colored by atom type; carbon, as the respective protein; nitrogen, blue; oxygen, red; sulfur, yellow; dashed black lines, hydrogen bonds or salt bridges.

.

.

.

^[2]

The structure and functional data of the human spliceosomal assembly factor Aar2 in complex with a core spliceosomal domain of the PRPF8 protein indicates a different function of human Aar2 in contrast to the yeast protein.

References

1. ↑ Preussner M, Santos KF, Alles J, Heroven C, Heyd F, Wahl MC, Weber G. Structural and functional investigation of the human snRNP assembly factor AAR2 in complex with the RNase H-like domain of PRPF8. Acta Crystallogr D Struct Biol. 2022 Nov 1;78(Pt 11):1373-1383. doi:, 10.1107/S2059798322009755. Epub 2022 Oct 27. PMID:36322420 doi:http://dx.doi.org/10.1107/S2059798322009755
2. ↑ Putnam AA, Jankowsky E. DEAD-box helicases as integrators of RNA, nucleotide and protein binding. Biochim Biophys Acta. 2013 Aug;1829(8):884-93. doi: 10.1016/j.bbagrm.2013.02.002., Epub 2013 Feb 15. PMID:23416748 doi:http://dx.doi.org/10.1016/j.bbagrm.2013.02.002