4NOD

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

4NOD の概要

• エントリーDOI: 10.2210/pdb4nod/pdb
• 分子名称: 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)
• 機能のキーワード: hmg, dna bending, tfb2m, mtrnap, bru substitution to hsp1, t19, transcription regulator-dna complex, transcription regulator/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Mitochondrion: Q00059
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 162551.02

構造登録者

Ngo, H.B.,Lovely, G.A.,Phillips, R.,Chan, D.C. (登録日: 2013-11-19, 公開日: 2014-01-22, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.897 Å)