3ISM

Crystal structure of the EndoG/EndoGI complex: Mechanism of EndoG inhibition

3ISM の概要

• エントリーDOI: 10.2210/pdb3ism/pdb
• 関連するPDBエントリー: 1QAE 1ZM8 2O3B
• 分子名称: CG8862, CG4930, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: endonuclease, endonuclease inhibitor complex, metal complex, hydrolase, hydrolase inhibitor-hydrolase complex, hydrolase inhibitor/hydrolase
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 101988.47

構造登録者

Loll, B.,Gebhardt, M.,Wahle, E.,Meinhart, A. (登録日: 2009-08-26, 公開日: 2009-09-08, 最終更新日: 2023-11-01)

主引用文献

Loll, B.,Gebhardt, M.,Wahle, E.,Meinhart, A.
Crystal structure of the EndoG/EndoGI complex: mechanism of EndoG inhibition.
Nucleic Acids Res., 37:7312-7320, 2009

PubMed Abstract: 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.

PubMed: 19783821
DOI: 10.1093/nar/gkp770

実験手法

X-RAY DIFFRACTION (2.2 Å)