4JK7

Open and closed forms of wild-type human PRP8 RNase H-like domain with bound Mg ion

Summary for 4JK7

• Entry DOI: 10.2210/pdb4jk7/pdb
• Related: 3ENB 4JK8 4JK9 4JKA 4JKB 4JKC 4JKD 4JKE 4JKF 4JKG 4JKH
• Descriptor: Pre-mRNA-processing-splicing factor 8, GLYCEROL, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: metalloprotein, conformational change, rna binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus speckle (By similarity): Q6P2Q9
• Total number of polymer chains: 2
• Total formula weight: 51487.64

Authors

Schellenberg, M.J.,Wu, T.,Ritchie, D.B.,Atta, K.,MacMillan, A.M. (deposition date: 2013-03-09, release date: 2013-05-22, Last modification date: 2023-09-20)

Primary citation

Schellenberg, M.J.,Wu, T.,Ritchie, D.B.,Fica, S.,Staley, J.P.,Atta, K.A.,Lapointe, P.,Macmillan, A.M.
A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation.
Nat.Struct.Mol.Biol., 20:728-734, 2013

PubMed Abstract: Splicing of pre-mRNAs in eukaryotes is catalyzed by the spliceosome, a large RNA-protein metalloenzyme. The catalytic center of the spliceosome involves a structure comprising the U2 and U6 snRNAs and includes a metal bound by U6 snRNA. The precise architecture of the splicesome active site, however, and the question of whether it includes protein components, remains unresolved. A wealth of evidence places the protein PRP8 at the heart of the spliceosome through assembly and catalysis. Here we provide evidence that the RNase H domain of PRP8 undergoes a conformational switch between the two steps of splicing, rationalizing yeast prp8 alleles that promote either the first or second step. We also show that this switch unmasks a metal-binding site involved in the second step. Together, these data establish that PRP8 is a metalloprotein that promotes exon ligation within the spliceosome.

PubMed: 23686287
DOI: 10.1038/nsmb.2556

Experimental method

X-RAY DIFFRACTION (1.4 Å)