8K4L

Crystal structure of NRF1 homodimer in complex with DNA

8K4L の概要

• エントリーDOI: 10.2210/pdb8k4l/pdb
• 分子名称: Nuclear respiratory factor 1, DNA (14-MER), GLYCEROL, ... (4 entities in total)
• 機能のキーワード: nuclear respiratory factor 1, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 60386.79

構造登録者

Liu, K.,Li, W.F.,Min, J.R. (登録日: 2023-07-19, 公開日: 2023-12-06, 最終更新日: 2024-02-07)

主引用文献

Liu, K.,Li, W.,Xiao, Y.,Lei, M.,Zhang, M.,Min, J.
Molecular mechanism of specific DNA sequence recognition by NRF1.
Nucleic Acids Res., 52:953-966, 2024

PubMed Abstract: Nuclear respiratory factor 1 (NRF1) regulates the expression of genes that are vital for mitochondrial biogenesis, respiration, and various other cellular processes. While NRF1 has been reported to bind specifically to GC-rich promoters as a homodimer, the precise molecular mechanism governing its recognition of target gene promoters has remained elusive. To unravel the recognition mechanism, we have determined the crystal structure of the NRF1 homodimer bound to an ATGCGCATGCGCAT dsDNA. In this complex, NRF1 utilizes a flexible linker to connect its dimerization domain (DD) and DNA binding domain (DBD). This configuration allows one NRF1 monomer to adopt a U-turn conformation, facilitating the homodimer to specifically bind to the two TGCGC motifs in the GCGCATGCGC consensus sequence from opposite directions. Strikingly, while the NRF1 DBD alone could also bind to the half-site (TGCGC) DNA of the consensus sequence, the cooperativity between DD and DBD is essential for the binding of the intact GCGCATGCGC sequence and the transcriptional activity of NRF1. Taken together, our results elucidate the molecular mechanism by which NRF1 recognizes specific DNA sequences in the promoters to regulate gene expression.

PubMed: 38055835
DOI: 10.1093/nar/gkad1162

実験手法

X-RAY DIFFRACTION (2.1 Å)