3E9L

Crystal Structure of Human Prp8, Residues 1755-2016

3E9L の概要

• エントリーDOI: 10.2210/pdb3e9l/pdb
• 関連するPDBエントリー: 3E9O 3E9P
• 分子名称: Pre-mRNA-processing-splicing factor 8, SODIUM ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: nucleotidyl transfer, disease mutation, mrna processing, mrna splicing, nucleus, phosphoprotein, retinitis pigmentosa, rna-binding, sensory transduction, spliceosome, vision, rna binding protein, splicing
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus speckle (By similarity): Q6P2Q9
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29593.67

構造登録者

Pena, V.,Rozov, A.,Wahl, M.C. (登録日: 2008-08-22, 公開日: 2008-10-07, 最終更新日: 2024-02-21)

主引用文献

Pena, V.,Rozov, A.,Fabrizio, P.,Luhrmann, R.,Wahl, M.C.
Structure and function of an RNase H domain at the heart of the spliceosome.
Embo J., 27:2929-2940, 2008

PubMed Abstract: Precursor-messenger RNA (pre-mRNA) splicing encompasses two sequential transesterification reactions in distinct active sites of the spliceosome that are transiently established by the interplay of small nuclear (sn) RNAs and spliceosomal proteins. Protein Prp8 is an active site component but the molecular mechanisms, by which it might facilitate splicing catalysis, are unknown. We have determined crystal structures of corresponding portions of yeast and human Prp8 that interact with functional regions of the pre-mRNA, revealing a phylogenetically conserved RNase H fold, augmented by Prp8-specific elements. Comparisons to RNase H-substrate complexes suggested how an RNA encompassing a 5'-splice site (SS) could bind relative to Prp8 residues, which on mutation, suppress splice defects in pre-mRNAs and snRNAs. A truncated RNase H-like active centre lies next to a known contact region of the 5'SS and directed mutagenesis confirmed that this centre is a functional hotspot. These data suggest that Prp8 employs an RNase H domain to help assemble and stabilize the spliceosomal catalytic core, coordinate the activities of other splicing factors and possibly participate in chemical catalysis of splicing.

PubMed: 18843295
DOI: 10.1038/emboj.2008.209

実験手法

X-RAY DIFFRACTION (1.95 Å)