5ZYT

Crystal structure of human MGME1 with 3' overhang double strand DNA3

Summary for 5ZYT

• Entry DOI: 10.2210/pdb5zyt/pdb
• Descriptor: Mitochondrial genome maintenance exonuclease 1, DNA (5'-D(P*CP*TP*TP*CP*TP*TP*CP*C)-3') (2 entities in total)
• Functional Keywords: human mgme1, dna complex, dna exonuclease, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 169805.43

Authors

Yang, C.,Gan, J. (deposition date: 2018-05-28, release date: 2018-09-19, Last modification date: 2024-03-27)

Primary citation

Yang, C.,Wu, R.,Liu, H.,Chen, Y.,Gao, Y.,Chen, X.,Li, Y.,Ma, J.,Li, J.,Gan, J.
Structural insights into DNA degradation by human mitochondrial nuclease MGME1
Nucleic Acids Res., 46:11075-11088, 2018

PubMed Abstract: Mitochondrial nucleases play important roles in accurate maintenance and correct metabolism of mtDNA, the own genetic materials of mitochondria that are passed exclusively from mother to child. MGME1 is a highly conserved DNase that was discovered recently. Mutations in MGME1-coding gene lead to severe mitochondrial syndromes characterized by external ophthalmoplegia, emaciation, and respiratory failure in humans. Unlike many other nucleases that are distributed in multiple cellular organelles, human MGME1 is a mitochondria-specific nuclease; therefore, it can serve as an ideal target for treating related syndromes. Here, we report one HsMGME1-Mn2+ complex and three different HsMGME1-DNA complex structures. In combination with in vitro cleavage assays, our structures reveal the detailed molecular basis for substrate DNA binding and/or unwinding by HsMGME1. Besides the conserved two-cation-assisted catalytic mechanism, structural analysis of HsMGME1 and comparison with homologous proteins also clarified substrate binding and cleavage directionalities of the DNA double-strand break repair complexes RecBCD and AddAB.

PubMed: 30247721
DOI: 10.1093/nar/gky855

Experimental method

X-RAY DIFFRACTION (2.702 Å)