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Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat

Abstract

The regulation of mitochondrial DNA (mtDNA) processes is slowly being characterized at a structural level. We present here crystal structures of human mitochondrial regulator mTERF, a transcription termination factor also implicated in replication pausing, in complex with double-stranded DNA oligonucleotides containing the tRNALeuUUR gene sequence. mTERF comprises nine left-handed helical tandem repeats that form a left-handed superhelix, the Zurdo domain.

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Figure 1: The mTERF Zurdo domain.
Figure 2: Protein-DNA interactions between mTERF and a 15-bp DNA.
Figure 3: Excision of TERF-I results in the reorganization of the protein structure.

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Acknowledgements

We acknowledge J. Colom for help during protein purification, G.M. Sheldrick for in-house data collection and S. Brockhauser for help with minikappa. This study was supported by the Spanish Ministerio de Ciencia e Innovación (grants BFU2006-09593, BFU2009-07134, BIO2009-10576, BFU2008-02372, FIS-PI070045), Generalitat de Catalunya (SGR2009-1366 and SGR2009-1309) and the European Community (LSHG-2006-031220). A.R.-C. and P.F.-M. hold fellowships from CSIC and the Ministerio de Ciencia e Innovación. P.B. holds a Ramon y Cajal contract. We acknowledge the Academy of Finland, Tampere University Hospital Medical Research Fund and Sigrid Juselius Foundation. We are grateful to European Molecular Biology Laboratory—Grenoble Outstation, the European Synchrotron Radiation Facility and the Automated Crystallography Platform (Barcelona Science Park) for their support.

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Authors and Affiliations

Authors

Contributions

N.J.-M. and C.A. contributed to cloning; N.J.-M. to protein production and crystallization; N.J.-M. and P.B. to SAXS studies; N.J.-M., I.U. and M.S. to X-ray structure determination; and N.J.-M., P.F.-M. and A.R.-C. to figure preparation. M.S. and M.C. provided materials and infrastructure. N.J.-M., H.T.J. and the rest of authors participated in manuscript writing and discussion. M.S. designed and supervised the project.

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Correspondence to Maria Solà.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 1161 kb)

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Jiménez-Menéndez, N., Fernández-Millán, P., Rubio-Cosials, A. et al. Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat. Nat Struct Mol Biol 17, 891–893 (2010). https://doi.org/10.1038/nsmb.1859

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