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Nucleic Acids Res. 2017 Jan 25;45(2):951-967. doi: 10.1093/nar/gkw1147. Epub 2016 Nov 29.

DNA structure directs positioning of the mitochondrial genome packaging protein Abf2p.

Author information

1
Structural MitoLab, Department of Structural Biology, "Maria de Maeztu" Unit of Excellence, Molecular Biology Institute Barcelona (IBMB-CSIC), Barcelona 08028, Spain.
2
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, Barcelona 08028, Spain.
3
Joint BSC-IRB Research Program in Computational Biology, Baldiri Reixac 10-12, Barcelona 08028, Spain.
4
Unitat de Polimorfisme i Calorimetria, Centres Científics i Tecnològics, University of Barcelona, Barcelona 08028, Spain.
5
Department of Biochemistry and Biomedicine, University of Barcelona, Barcelona 08028, Spain.
6
Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluis Companys 23, Barcelona 08010, Spain.
7
Molecular Genomics Department, Molecular Biology Institute Barcelona (IBMB-CSIC), Barcelona, 08028, Spain.
8
Structural MitoLab, Department of Structural Biology, "Maria de Maeztu" Unit of Excellence, Molecular Biology Institute Barcelona (IBMB-CSIC), Barcelona 08028, Spain maria.sola@ibmb.csic.es.

Abstract

The mitochondrial genome (mtDNA) is assembled into nucleo-protein structures termed nucleoids and maintained differently compared to nuclear DNA, the involved molecular basis remaining poorly understood. In yeast (Saccharomyces cerevisiae), mtDNA is a ∼80 kbp linear molecule and Abf2p, a double HMG-box protein, packages and maintains it. The protein binds DNA in a non-sequence-specific manner, but displays a distinct 'phased-binding' at specific DNA sequences containing poly-adenine tracts (A-tracts). We present here two crystal structures of Abf2p in complex with mtDNA-derived fragments bearing A-tracts. Each HMG-box of Abf2p induces a 90° bend in the contacted DNA, causing an overall U-turn. Together with previous data, this suggests that U-turn formation is the universal mechanism underlying mtDNA compaction induced by HMG-box proteins. Combining this structural information with mutational, biophysical and computational analyses, we reveal a unique DNA binding mechanism for Abf2p where a characteristic N-terminal flag and helix are crucial for mtDNA maintenance. Additionally, we provide the molecular basis for A-tract mediated exclusion of Abf2p binding. Due to high prevalence of A-tracts in yeast mtDNA, this has critical relevance for nucleoid architecture. Therefore, an unprecedented A-tract mediated protein positioning mechanism regulates DNA packaging proteins in the mitochondria, and in combination with DNA-bending and U-turn formation, governs mtDNA compaction.

PMID:
27899643
PMCID:
PMC5314765
DOI:
10.1093/nar/gkw1147
[Indexed for MEDLINE]
Free PMC Article

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