2OG4

Structure of an expanded Jab1-MPN-like domain of splicing factor Prp8p from yeast

2OG4 の概要

• エントリーDOI: 10.2210/pdb2og4/pdb
• 分子名称: Pre-mRNA-splicing factor 8 (2 entities in total)
• 機能のキーワード: isopeptidase, jab1/mpn domain, pre-mrna splicing, protein-protein interaction, prp8p, pseudoenzyme, spliceosome activation, u5-200k protein, protein binding
• 由来する生物種: Saccharomyces cerevisiae
• 細胞内の位置: Nucleus : P33334
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28743.52

構造登録者

Pena, V.,Liu, S.,Luehrmann, R.,Wahl, M.C. (登録日: 2007-01-05, 公開日: 2007-03-13, 最終更新日: 2023-12-27)

主引用文献

Pena, V.,Liu, S.,Bujnicki, J.M.,Luhrmann, R.,Wahl, M.C.
Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa.
Mol.Cell, 25:615-624, 2007

PubMed Abstract: Protein Prp8 interacts with several other spliceosomal proteins, snRNAs, and the pre-mRNA and thereby organizes the active site(s) of the spliceosome. The DEAD-box protein Brr2 and the GTPase Snu114 bind to the Prp8 C terminus, a region where mutations in human Prp8 are linked to the RP13 form of Retinitis pigmentosa. We show crystallographically that the C-terminal domain of yeast Prp8p exhibits a Jab1/MPN-like core known from deubiquitinating enzymes. Insertions and terminal appendices are grafted onto this core, covering a putative isopeptidase center whose metal binding site is additionally impaired. Targeted yeast-two-hybrid analyses show that the RP13-linked region in the C-terminal appendix of human Prp8 is essential for binding of human Brr2 and Snu114, and that RP13 point mutations in this fragment weaken these interactions. We conclude that the expanded Prp8 Jab1/MPN domain represents a pseudoenzyme converted into a protein-protein interaction platform and that dysfunction of this platform underlies Retinitis pigmentosa.

PubMed: 17317632
DOI: 10.1016/j.molcel.2007.01.023

実験手法

X-RAY DIFFRACTION (2 Å)