9J1O

Mouse Spi-B Ets domain in complex with DNA containing GGAA sequence

Summary for 9J1O

• Entry DOI: 10.2210/pdb9j1o/pdb
• Related: 9J1N
• Descriptor: DNA (5'-D(*(3D1)P*TP*GP*AP*AP*AP*AP*GP*GP*GP*AP*AP*TP*TP*GP*G)-3'), DNA (5'-D(*(THM)P*CP*CP*AP*AP*TP*TP*CP*CP*CP*TP*TP*TP*TP*CP*A)-3'), Transcription factor Spi-B, ... (7 entities in total)
• Functional Keywords: dna binding, transcription, immune system, dna binding protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 3
• Total formula weight: 22242.23

Authors

Nonaka, Y.,Kamitori, S. (deposition date: 2024-08-05, release date: 2025-06-18)

Primary citation

Nonaka, Y.,Hoshino, K.,Nakamura, T.,Kamitori, S.
Structural analysis of Spi-B DNA-binding Ets domain recognizing 5'-AGAA-3' and 5'-GGAA-3' sequences.
Biochem.Biophys.Res.Commun., 749:151354-151354, 2025

PubMed Abstract: Plasmacytoid dendritic cells produce large amounts of type-I interferon (IFN-I) upon sensing nucleic acid components of pathogens by Toll-like receptors (TLR7 and TLR9). The transcription factor Spi-B has the DNA-binding Ets domain, and transactivates the Ifna4 promoter co-operatively with IFN regulatory factor-7 (IRF-7) for TLR7/TLR9-induced IFN-I production. Spi-B associates with IRF-7, and activates transcription by binding to the 5'-AGAA-3' sequence, being different from 5'-GGAA-3', known as the Ets domain recognition sequence. To understand the molecular mechanism for the co-operative transactivation of the Ifna4 promoter by Spi-B and IRF-7, we performed X-ray structural determination of the Spi-B Ets domain in complex with target DNAs, including 5'-AGAA-3' and 5'-GGAA-3' sequences. Furthermore, we conducted a modeling study of the complex of the Spi-B and IRF-7 with Ifna4 promoter DNA. X-ray structures showed that the binding of the Spi-B Ets domain induces a kink in DNA at the recognition sequence, and a more kinked DNA structure was observed in 5'-AGAA-3' than 5'-GGAA-3'. A modeling study showed that the Spi-B-induced kinked DNA structure in 5'-AGAA-3' is favorable for Spi-B and IRF-7 to approach each other for association on DNA.

PubMed: 39892964
DOI: 10.1016/j.bbrc.2025.151354

Experimental method

X-RAY DIFFRACTION (2.23 Å)