8K8C

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

Summary for 8K8C

• Entry DOI: 10.2210/pdb8k8c/pdb
• Descriptor: 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)
• Functional Keywords: c/ebpalpha, dna binding, bzip, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 22806.86

Authors

Min, J.R.,Chen, S.Z.,Liu, K. (deposition date: 2023-07-29, release date: 2024-03-06, Last modification date: 2024-03-27)

Primary citation

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 demonstrate a shared preference for the TTACGTAA sequence. Furthermore, our study revealed that disease-associated mutations within the NFIL3 bZIP domain result 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

Experimental method

X-RAY DIFFRACTION (2.06 Å)