8J0R

Structure of human TFAP2A in complex with DNA

8J0R の概要

• エントリーDOI: 10.2210/pdb8j0r/pdb
• 分子名称: Transcription factor AP-2-alpha, DNA (5'-D(*CP*TP*GP*CP*CP*TP*CP*AP*GP*GP*CP*AP*C)-3'), DNA (5'-D(*GP*TP*GP*CP*CP*TP*GP*AP*GP*GP*CP*AP*G)-3'), ... (8 entities in total)
• 機能のキーワード: tfap2 family, dna binding protein/dna, dna binding protein-dna complex
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 56869.29

構造登録者

Liu, K.,Xiao, Y.Q.,Li, W.F.,Min, J.R. (登録日: 2023-04-11, 公開日: 2023-07-05, 最終更新日: 2023-09-06)

主引用文献

Liu, K.,Xiao, Y.,Gan, L.,Li, W.,Zhang, J.,Min, J.
Structural basis for specific DNA sequence motif recognition by the TFAP2 transcription factors.
Nucleic Acids Res., 51:8270-8282, 2023

PubMed Abstract: The TFAP2 family regulates gene expression during differentiation, development, and organogenesis, and includes five homologs in humans. They all possess a highly conserved DNA binding domain (DBD) followed by a helix-span-helix (HSH) domain. The DBD-HSH tandem domain specifically binds to a GCC(N3)GGC consensus sequence, but the precise recognition mechanisms remain unclear. Here, we found that TFAP2 preferred binding to the GCC(N3)GGC sequence, and the pseudo-palindromic GCC and GGC motifs and the length of the central spacer between the two motifs determined their binding specificity. Structural studies revealed that the two flat amphipathic α-helical HSH domains of TFAP2A stacked with each other to form a dimer via hydrophobic interactions, while the stabilized loops from both DBD domains inserted into two neighboring major grooves of the DNA duplex to form base-specific interactions. This specific DNA binding mechanism controlled the length of the central spacer and determined the DNA sequence specificity of TFAP2. Mutations of the TFAP2 proteins are implicated in various diseases. We illustrated that reduction or disruption of the DNA binding ability of the TFAP2 proteins is the primary cause of TFAP2 mutation-associated diseases. Thus, our findings also offer valuable insights into the pathogenesis of disease-associated mutations in TFAP2 proteins.

PubMed: 37409559
DOI: 10.1093/nar/gkad583

実験手法

X-RAY DIFFRACTION (2.1 Å)