ArticleNature communications2025
The ALX4 dimer structure provides insight into how disease alleles impact function.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.Nature communications · 2026Article
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.bioRxiv : the preprint server for biology · 2025Article
- The ALX4 dimer structure provides insight into how disease alleles impact function.Nature communications · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
How homeodomain proteins gain sufficient DNA binding specificity to regulate diverse processes is a long-standing question. Here, we determine how the ALX4 Paired-like protein achieves DNA binding specificity for a TAAT-NNN-ATTA dimer site. We first show that ALX4 binds this motif independently of its co-factor, TWIST1, in cranial neural crest cells. Structural analysis identifies seven ALX4 residues that participate in dimer binding, many of which are conserved across the Paired-like family, but not other homeodomain proteins. Unexpectedly, the two ALX4 proteins within the dimer use distinct residues to form asymmetric protein-protein and protein-DNA interactions and mediate cooperativity. Moreover, we find that ALX4 cooperativity is required for transcriptional activation and that ALX4 disease variants cause distinct molecular defects that include loss of cooperativity. These findings provide insights into how Paired-like factors gain DNA specificity and show how disease variants can be stratified based on their molecular defects.
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