4NOD: Distinct Structural Features Of Tfam Drive Mitochondrial Dna Packaging Versus Transcriptional Activation

TFAM (transcription factor A, mitochondrial) is a DNA-binding protein that activates transcription at the two major promoters of mitochondrial DNA (mtDNA)-the light strand promoter (LSP) and the heavy strand promoter 1 (HSP1). Equally important, it coats and packages the mitochondrial genome. TFAM has been shown to impose a U-turn on LSP DNA; however, whether this distortion is relevant at other sites is unknown. Here we present crystal structures of TFAM bound to HSP1 and to nonspecific DNA. In both, TFAM similarly distorts the DNA into a U-turn. Yet, TFAM binds to HSP1 in the opposite orientation from LSP explaining why transcription from LSP requires DNA bending, whereas transcription at HSP1 does not. Moreover, the crystal structures reveal dimerization of DNA-bound TFAM. This dimerization is dispensable for DNA bending and transcriptional activation but is important in DNA compaction. We propose that TFAM dimerization enhances mitochondrial DNA compaction by promoting looping of the DNA.
PDB ID: 4NODDownload
MMDB ID: 116902
PDB Deposition Date: 2013/11/19
Updated in MMDB: 2014/02
Experimental Method:
x-ray diffraction
Resolution: 2.9  Å
Source Organism:
Similar Structures:
Biological Unit for 4NOD: trimeric; determined by author and by software (PISA)
Molecular Components in 4NOD
Label Count Molecule
Protein (1 molecule)
Transcription Factor A, Mitochondrial(Gene symbol: TFAM)
Molecule annotation
Nucleotides(2 molecules)
5'-d(*tp*tp*gp*gp*gp*gp*tp*ap*tp*gp*gp*gp*gp*cp*tp*tp*gp*gp *(bru)p*tp*gp*g)-3'
Molecule annotation
5'-d(*cp*cp*ap*ap*cp*cp*ap*ap*gp*cp*cp*cp*cp*ap*tp*ap*cp*cp *cp*cp*ap*a)-3'
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB