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Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter

A Corrigendum to this article was published on 05 March 2012

This article has been updated

Abstract

Human mitochondrial transcription factor A, TFAM, is essential for mitochondrial DNA packaging and maintenance and also has a crucial role in transcription. Crystallographic analysis of TFAM in complex with an oligonucleotide containing the mitochondrial light strand promoter (LSP) revealed two high-mobility group (HMG) protein domains that, through different DNA recognition properties, intercalate residues at two inverted DNA motifs. This induced an overall DNA bend of ~180°, stabilized by the interdomain linker. This U-turn allows the TFAM C-terminal tail, which recruits the transcription machinery, to approach the initiation site, despite contacting a distant DNA sequence. We also ascertained that structured protein regions contacting DNA in the crystal were highly flexible in solution in the absence of DNA. Our data suggest that TFAM bends LSP to create an optimal DNA arrangement for transcriptional initiation while facilitating DNA compaction elsewhere in the genome.

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Figure 1: TFAM–LSP-22 complex.
Figure 2: Comparison of HMG1 and HMG2 boxes and their contacts with DNA.
Figure 3: Close-up views of three TFAM areas contacting LSP-22 (see top scheme for reference).
Figure 4: SAXS analysis of unbound TFAM.
Figure 5: Working model for the role of TFAM in transcriptional activation at LSP.

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  • 20 December 2011

    In the version of this article initially published, the name of the second author was misspelled. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank C. Silva and J. Colom for technical support. This study was supported by the Ministerio de Ciencia e Innovación (grants BFU2006-09593 to M.S., BFU2009-07134 to M.S., BFU2008-02372 to M.C., CSD2006-00023), Generalitat de Catalunya (SGR2009-1366 to M.S., SGR2009-1309 to M.C., SGR2009-1352 to P.B.), the European Union (FP7-HEALTH-2010-261460 to M.S., FP7-BioNMR-2010-261863 to P.B.), and Instituto de Salud Carlos III-FIS-PI 10/00662. The Centro de Investigación Biomédica en Red de Enfermedades Raras is an initiative of the Instituto de Salud Carlos III. A.R.-C., J.F.S., N.J.-M. and P.F.-M. hold or held fellowships from Consejo Superior de Investigaciones Científicas, MICINN and Cusanswerk-Bischöfliche Studienförderung. H.T.J. is supported by Academy of Finland, Tampere University Hospital Medical Research Fund and Sigrid Juselius Foundation. We also thank the European Molecular Biology Laboratory (EMBL)-Grenoble and EMBL-Hamburg Outstations, the European Synchrotron Radiation Facility in Grenoble and the Automated Crystallography Platform (Barcelona Science Park) for their support.

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

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Correspondence to Maria Solà.

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Rubio-Cosials, A., Sydow, J., Jiménez-Menéndez, N. et al. Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. Nat Struct Mol Biol 18, 1281–1289 (2011). https://doi.org/10.1038/nsmb.2160

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