9QKY

The structure of the DNA-binding domain of Nuclear Factor 1 X bound to NFI consensus DNA sequence

9QKY の概要

• エントリーDOI: 10.2210/pdb9qky/pdb
• EMDBエントリー: 53223
• 分子名称: Nuclear factor 1 X-type, DNA (31-MER), ZINC ION, ... (4 entities in total)
• 機能のキーワード: transcription factor, dna-binding domain, mh1-like domain, ccch motif, zinc ion binding site, transcription
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 247431.71

構造登録者

Tiberi, M.,Nardini, M.,Chaves-Sanjuan, A.,Gourlay, L.J.,Bonnet, D.M.V. (登録日: 2025-03-20, 公開日: 2025-09-17, 最終更新日: 2025-12-24)

主引用文献

Tiberi, M.,Lapi, M.,Gourlay, L.J.,Chaves-Sanjuan, A.,Polentarutti, M.,Demitri, N.,Cavinato, M.,Bonnet, D.M.V.,Taglietti, V.,Righetti, A.,Sala, R.,Cauteruccio, S.,Kumawat, A.,Russo, R.,Barbiroli, A.G.,Gnesutta, N.,Camilloni, C.,Bolognesi, M.,Messina, G.,Nardini, M.
Structural basis of Nuclear Factor 1-X DNA recognition provides prototypic insight into the NFI family.
Nat Commun, 16:10170-10170, 2025

PubMed Abstract: Nuclear Factor I (NFI) proteins are involved in adenovirus DNA replication and regulate gene transcription, stem cell proliferation, and differentiation. They play key roles in development, cancer, and congenital disorders. Within the NFI family, NFI-X is critical for neural stem cell biology, hematopoiesis, muscle development, muscular dystrophies, and oncogenesis. Here, we present the structural characterization of the NFI transcription factor NFI-X, both alone and bound to its consensus palindromic DNA site. Our analyses reveal a MH1-like fold within NFI-X DNA-binding domain (DBD) and identify crucial structural determinants for activity, such as a Zn²⁺ binding site, dimeric assembly, and DNA-binding specificity. Given the ~85% sequence identity within the NFI DBDs, our structural data are prototypic for the entire family, a NFI Rosetta Stone that allows decoding a wealth of biochemical and functional data and provides a precise target for drug design in a wider disease context.

PubMed: 41261119
DOI: 10.1038/s41467-025-65186-0

実験手法

ELECTRON MICROSCOPY (3.86 Å)