Crystal structure of Prp8 reveals active site cavity of the spliceosome

被引：179

作者：

Galej, Wojciech P. ^{[1
]}

Oubridge, Chris ^{[1
]}

Newman, Andrew J. ^{[1
]}

Nagai, Kiyoshi ^{[1
]}

机构：

[1] MRC Lab Mol Biol, Cambridge CB2 0QH, England

来源：

NATURE | 2013年 / 493卷 / 7434期

基金：

英国医学研究理事会;

关键词：

SPLICING FACTOR PRP8; SMALL NUCLEAR RNAS; MESSENGER-RNA; U5; SNRNP; SECONDARY-STRUCTURE; U6; SNRNA; CROSS-LINKING; PROTEIN; DOMAIN; MECHANISM;

D O I：

10.1038/nature11843

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The active centre of the spliceosome consists of an intricate network formed by U5, U2 and U6 small nuclear RNAs, and a pre-messenger-RNA substrate. Prp8, a component of the U5 small nuclear ribonucleoprotein particle, crosslinks extensively with this RNA catalytic core. Here we present the crystal structure of yeast Prp8 (residues 885-2413) in complex with Aar2, a U5 small nuclear ribonucleoprotein particle assembly factor. The structure reveals tightly associated domains of Prp8 resembling a bacterial group II intron reverse transcriptase and a type II restriction endonuclease. Suppressors of splice-site mutations, and an intron branch-point crosslink, map to a large cavity formed by the reverse transcriptase thumb, and the endonuclease-like and RNaseH-like domains. This cavity is large enough to accommodate the catalytic core of group II intron RNA. The structure provides crucial insights into the architecture of the spliceosome active site, and reinforces the notion that nuclear pre-mRNA splicing and group II intron splicing have a common origin.

引用

页码：638 / +

页数：7

共 70 条

[1] The human U5-220kD protein (hPrp8) forms a stable RNA-free complex with several US-specific proteins, including an RNA unwindase, a homologue of ribosomal elongation factor EF-2, and a novel WD-40 protein [J].