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

Created on 07 Aug 2026

Authors

Aiswarya Mohandas, Hyun Joo Nam

Published in

Acta crystallographica. Section F, Structural biology communications. Sep 01, 2026. Epub Sep 01, 2026.

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.

PMID:
42565819
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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