36NB

Crystal structure of the NKX2-1 homeodomain bound to a palindromic DNA recognition sequence

Summary for 36NB

• Entry DOI: 10.2210/pdb36nb/pdb
• Descriptor: Homeobox protein Nkx-2.1, DAN TCAAGTGGGCCCCACTTGA, DNA TCAAGTGGGGCCCACTTGA, ... (4 entities in total)
• Functional Keywords: nkx2-1, homeodomain, nk2 element, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 53266.05

Authors

Nam, H.J. (deposition date: 2026-06-19, release date: 2026-08-19, Last modification date: 2026-09-09)

Primary citation

Mohandas, A.,Nam, H.J.
Crystal structure of the NKX2-1 homeodomain bound to a palindromic DNA recognition sequence.
Acta Crystallogr.,Sect.F, 82:295-300, 2026

PubMed Abstract: NKX2-1 (thyroid transcription factor 1, TTF-1) is a homeodomain transcription factor that plays critical roles in the development and function of the thyroid, lung and forebrain. Here, we report the crystal structure of the NKX2-1 homeodomain bound to a 19 bp DNA duplex containing two palindromically arranged NK2-recognition motifs, refined to 3.26 Å resolution. The structure reveals two homeodomains bound to a single DNA duplex and demonstrates that the overall fold and DNA-binding interactions are highly conserved relative to those of NKX2-5. Comparison with NKX2-5 further shows that the amino-acid residues that differ between the two homeodomains are located away from the protein-DNA interface, suggesting that functional differences between these transcription factors are unlikely to arise from distinct DNA-recognition mechanisms. These findings provide a structural framework for understanding DNA recognition by NKX2-1 and for interpreting the effects of pathogenic variants within its homeodomain.

PubMed: 42565819
DOI: 10.1107/S2053230X26007466

Experimental method

X-RAY DIFFRACTION (3.26 Å)