Structure of the archaeal Kae1/Bud32 fusion protein MJ1130: a model for the eukaryotic EKC/KEOPS subcomplex
Structure of the archaeal Kae1/Bud32 fusion protein MJ1130: a model for the eukaryotic EKC/KEOPS subcomplex
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DOI：
10.1038/emboj.2008.157
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发表时间：
2008-09-03
期刊：
影响因子：
11.4
通讯作者：
van Tilbeurgh, Herman
中科院分区：
文献类型：
--
作者：
Hecker, Arnaud;Lopreiato, Raffaele;van Tilbeurgh, Herman
EKC/KEOPS酵母复合物参与端粒的维持和转录。Bud 32 p和激酶相关的内肽酶1（Kae 1 p）组成的复合物是完全保守的真核生物和古细菌。它们的基因融合在几个古细菌基因组中，表明它们在物理上相互作用。本文报道了詹氏甲烷球菌Kae 1/Bud 32融合蛋白MJ 1130的结构。Kae 1是一种具有ASKHA折叠的铁蛋白，Bud 32是一种非典型的小RIO型激酶。结构MJ 1130表明与Kae 1的结合使Bud 32激酶保持在非活性状态。我们确实表明，酵母Kae 1 p抑制酵母Bud 32 p的激酶活性。MjKae 1和MjBud 32之间广泛的保守相互作用表明，Kae 1 p和Bud 32 p直接在酵母和古细菌中相互作用。在酵母复合物的背景下破坏Kae 1 p/Bud 32 p相互作用的突变在体内和体外具有显著的效果，类似于用相应组分的缺失突变观察到的那些。酵母中Kae 1 p和Bud 32 p之间的直接相互作用对于EKC/KEOPS的转录和端粒稳态功能都是必需的。
The EKC/KEOPS yeast complex is involved in telomere maintenance and transcription. The Bud32p and kinase-associated endopeptidase 1 (Kae1p) components of the complex are totally conserved in eukarya and archaea. Their genes are fused in several archaeal genomes, suggesting that they physically interact. We report here the structure of the Methanocaldococcus jannaschii Kae1/Bud32 fusion protein MJ1130. Kae1 is an iron protein with an ASKHA fold and Bud32 is an atypical small RIO-type kinase. The structure MJ1130 suggests that association with Kae1 maintains the Bud32 kinase in an inactive state. We indeed show that yeast Kae1p represses the kinase activity of yeast Bud32p. Extensive conserved interactions between MjKae1 and MjBud32 suggest that Kae1p and Bud32p directly interact in both yeast and archaea. Mutations that disrupt the Kae1p/Bud32p interaction in the context of the yeast complex have dramatic effects in vivo and in vitro, similar to those observed with deletion mutations of the respective components. Direct interaction between Kae1p and Bud32p in yeast is required both for the transcription and the telomere homeostasis function of EKC/KEOPS.