4NOD

Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation

Summary for 4NOD

• Entry DOI: 10.2210/pdb4nod/pdb
• Descriptor: Transcription factor A, mitochondrial, 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', 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' (3 entities in total)
• Functional Keywords: hmg, dna bending, tfb2m, mtrnap, bru substitution to hsp1, t19, transcription regulator-dna complex, transcription regulator/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion: Q00059
• Total number of polymer chains: 12
• Total formula weight: 162551.02

Authors

Ngo, H.B.,Lovely, G.A.,Phillips, R.,Chan, D.C. (deposition date: 2013-11-19, release date: 2014-01-22, Last modification date: 2023-09-20)

Primary citation

Ngo, H.B.,Lovely, G.A.,Phillips, R.,Chan, D.C.
Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation.
Nat Commun, 5:3077-3077, 2014

PubMed Abstract: 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.

PubMed: 24435062
DOI: 10.1038/ncomms4077

Experimental method

X-RAY DIFFRACTION (2.897 Å)