8K8C

Crystal structure of C/EBPalpha BZIP domain bound to a high affinity DNA

8K8C の概要

• エントリーDOI: 10.2210/pdb8k8c/pdb
• 分子名称: CCAAT/enhancer-binding protein alpha, DNA (5'-D(*CP*AP*TP*TP*AP*CP*GP*TP*AP*AP*TP*GP*A)-3'), DNA (5'-D(*CP*AP*TP*TP*AP*CP*GP*TP*AP*AP*TP*GP*T)-3'), ... (5 entities in total)
• 機能のキーワード: c/ebpalpha, dna binding, bzip, 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: 22806.86

構造登録者

Min, J.R.,Chen, S.Z.,Liu, K. (登録日: 2023-07-29, 公開日: 2024-03-06, 最終更新日: 2024-03-27)

主引用文献

Chen, S.,Lei, M.,Liu, K.,Min, J.
Structural basis for specific DNA sequence recognition by the transcription factor NFIL3.
J.Biol.Chem., 300:105776-105776, 2024

PubMed Abstract: The CCAAT/enhancer-binding proteins (C/EBPs) constitute a family of pivotal transcription factors involved in tissue development, cellular function, proliferation, and differentiation. NFIL3, as one of them, plays an important role in regulating immune cell differentiation, circadian clock system and neural regeneration, yet its specific DNA recognition mechanism remains enigmatic. In this study, we showed by the ITC binding experiments that NFIL3 prefers to bind to the TTACGTAA DNA motif. Our structural studies revealed that the α-helical NFIL3 bZIP domain dimerizes through its leucine zipper region, and binds to DNA via its basic region. The two basic regions of the NFIL3 bZIP dimer were pushed apart upon binding to DNA, facilitating the snug accommodation of the two basic regions within the major grooves of the DNA. Remarkably, our binding and structural data also revealed that both NFIL3 and C/EBPα/β demonstrated a shared preference for the TTACGTAA sequence. Furthermore, our study revealed that disease-associated mutations within the NFIL3 bZIP domain resulted in either reduction or complete disruption of its DNA binding ability. These discoveries not only provide valuable insights into the DNA binding mechanisms of NFIL3 but also elucidate the causal role of NFIL3 mutations in disease pathogenesis.

PubMed: 38382670
DOI: 10.1016/j.jbc.2024.105776

実験手法

X-RAY DIFFRACTION (2.06 Å)