Crystal structure of the EndoG/EndoGI complex: mechanism of EndoG inhibition.
Crystal structure of the EndoG/EndoGI complex: mechanism of EndoG inhibition.
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DOI：
10.1093/nar/gkp770
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发表时间：
2009-11
影响因子：
14.9
通讯作者：
Meinhart A
中科院分区：
文献类型：
--
作者：
Loll B;Gebhardt M;Wahle E;Meinhart A
EndoG是一种普遍存在的核酸酶，在细胞凋亡过程中易位到细胞核中参与DNA降解。这种酶可以切割双链和单链DNA和RNA。相关的核酸酶存在于真核生物和原核生物中，它们已经进化出复杂的机制来保护基因组免受自拮抗核酸酶的活性。常见的抑制机制是分泌、隔离到单独的细胞室或与蛋白质抑制剂结合。尽管EndoG通过区隔化进入线粒体膜间隙而沉默，但在果蝇非凋亡条件下，核定位蛋白抑制剂保护细胞多核苷酸不被杂散的EndoG降解。在这里，我们报道了EndoG及其抑制剂EndoGI复合物的第一个三维结构。尽管其抑制机制与细菌蛋白抑制剂相似，但EndoGI是独立于一般的蛋白-蛋白相互作用模块进化而来的。EndoGI是一种双结构域蛋白，结合EndoG的两个单体的活性位点，EndoG夹在EndoGI之间。由于真核生物EndoG同源物的氨基酸序列高度保守，因此该模型一般适用于真核生物二聚体EndoG。该结构表明，EndoG的两个活性位点在分子表面占据最遥远的空间位置，因此不太可能进行一致的底物加工。
EndoG is a ubiquitous nuclease that is translocated into the nucleus during apoptosis to participate in DNA degradation. The enzyme cleaves double- and single-stranded DNA and RNA. Related nucleases are found in eukaryotes and prokaryotes, which have evolved sophisticated mechanisms for genome protection against self-antagonizing nuclease activity. Common mechanisms of inhibition are secretion, sequestration into a separate cellular compartment or by binding to protein inhibitors. Although EndoG is silenced by compartmentalization into the mitochondrial intermembrane space, a nucleus-localized protein inhibitor protects cellular polynucleotides from degradation by stray EndoG under non-apoptotic conditions in Drosophila. Here, we report the first three-dimensional structure of EndoG in complex with its inhibitor EndoGI. Although the mechanism of inhibition is reminiscent of bacterial protein inhibitors, EndoGI has evolved independently from a generic protein-protein interaction module. EndoGI is a two-domain protein that binds the active sites of two monomers of EndoG, with EndoG being sandwiched between EndoGI. Since the amino acid sequences of eukaryotic EndoG homologues are highly conserved, this model is valid for eukaryotic dimeric EndoG in general. The structure indicates that the two active sites of EndoG occupy the most remote spatial position possible at the molecular surface and a concerted substrate processing is unlikely.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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