3ISM

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

Summary for 3ISM

• Entry DOI: 10.2210/pdb3ism/pdb
• Related: 1QAE 1ZM8 2O3B
• Descriptor: CG8862, CG4930, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: endonuclease, endonuclease inhibitor complex, metal complex, hydrolase, hydrolase inhibitor-hydrolase complex, hydrolase inhibitor/hydrolase
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 3
• Total formula weight: 101988.47

Authors

Loll, B.,Gebhardt, M.,Wahle, E.,Meinhart, A. (deposition date: 2009-08-26, release date: 2009-09-08, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)