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Crystal structure of ZBTB20 in complex with mouse AFP promoter
Structural highlights
DiseaseZBT20_HUMAN Intellectual disability-cataracts-calcified pinnae-myopathy syndrome. The disease is caused by variants affecting the gene represented in this entry. FunctionZBT20_HUMAN May be a transcription factor that may be involved in hematopoiesis, oncogenesis, and immune responses (PubMed:11352661). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (By similarity).[UniProtKB:Q8K0L9][1] Publication Abstract from PubMedZBTB20, a C2H2 zinc finger and broad-complex, tramtrack and bric-a-brac (BTB) domain-containing protein, is crucial for organ development and metabolic homeostasis. Its functionality is dependent on its DNA-binding zinc fingers, and heterozygous mutations within these regions are linked to Primrose syndrome, which is characterized by various physical and developmental abnormalities. However, the molecular basis underlying ZBTB20 zinc finger recognition of DNA remains largely unknown. Here, we present the crystal structure of ZBTB20 zinc fingers 1-4 (ZF1-4) in complex with the mouse alpha-fetoprotein (AFP) promoter in the region spanning positions -104 to -90. In combination with calorimetric analysis, we established that ZF1-3 is essential for the recognition of the AFP promoter and identified key residues involved in DNA binding. Furthermore, our data allow us to correlate Primrose syndrome mutations with alterations in DNA-binding efficacy. Overall, our study provides mechanistic insights into the physiological and pathological roles of ZBTB20 zinc fingers. Structural insights into ZBTB20 action at the AFP promoter.,Yang L, Xie H, Wan X, Li M, Lv M, Duan Y, Shi Y, Zhang WJ, Li F Structure. 2025 Aug 7;33(8):1398-1407.e2. doi: 10.1016/j.str.2025.05.009. Epub , 2025 Jun 9. PMID:40494351[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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