Referencia

PMID:22037172

Autores

Rubio-Cosials A, Sidow JF, Jiménez-Menéndez N, Fernández-Millán P, Montoya J, Jacobs HT, Coll M, Bernadó P, Solà M.

Resumen

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.

Descripción

El factor de transcripción mitocondrial humano, TFAM, participa en la transcripción del ADN mitocondrial y en su empaquetamiento. La estructura cristalográfica del complejo TFAM con el promotor LSP muestra cómo dos dominios HMGbox unen el ADN y, juntamente con un linker helicoidal inter-dominio, doblan el DNA 180º, posicionando la cola C-terminal de TFAM cerca del sitio de la iniciación. El análisis de TFAM en solución muestra como el linker es altamente flexible y que se estructura tras la unión con el DNA.

Foto grupo Diciembre

REFERENCIA DEL GRUPO INVESTIGADOR
El objetivo de nuestro grupo es entender la base estructural de la regulación del ADN mitocondrial. En el laboratorio, se expresan y purifican proteínas, solas o en complejo con otras macromoléculas (proteínas, ADN), para caracterizar su función mediante ensayos bioquímicos y cristalográficos. Los resultados se complementan con técnicas de otras especialidades, en colaboración con otros grupos, para tener así una visión multidisciplinar lo más amplia posible del objeto de estudio.

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