12UL

BCL11B ZF2-3 in Complex with a DNA Sequence Observed in the Human Globin Locus Containing Motif TGTCCA (Oligo 3-4)

12UL の概要

• エントリーDOI: 10.2210/pdb12ul/pdb
• 分子名称: Strand Top, Strand Bottom, B-cell lymphoma/leukemia 11B, ... (6 entities in total)
• 機能のキーワード: transcription factor, dna binding, transcription, transcription-dna complex, globin locus, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 15649.88

構造登録者

Horton, J.R.,Cheng, X.,Zhou, J.,Lee, J. (登録日: 2026-04-19, 公開日: 2026-07-01)

主引用文献

Lee, J.,Zhou, J.,Horton, J.R.,Yu, M.,Muoghalu, M.D.,Khan, F.A.,Zhang, X.,Huang, Y.,Blumenthal, R.M.,Zhang, X.,Cheng, X.
Bipartite DNA binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs.
Biorxiv, 2026

PubMed Abstract: B-cell leukemia/lymphoma 11B (BCL11B), despite its name, is a key regulator of T-cell development, specification, and T-cell malignancies. BCL11B contains a bipartite DNA binding domain composed of two C2H2 zinc finger arrays: low-affinity ZF2-3 and high affinity ZF4-6. These arrays function as homotypic modules that recognize similar six-nucleotide motifs, TG(N)CC(C/T/A), as seven of the eight DNA base-contacting residues are conserved between them. The most conserved interactions involve GG dinucleotides, contacted by arginine and lysine residues at key base-interacting positions in ZF3 and ZF5. The two ZF arrays are connected by a long ~300-residue linker that provides flexibility in how the arrays engage DNA, allowing ZF2-3 and ZF4-6 binding to the same or opposite strands with variable orientation, spacing and positioning along the DNA. This extended linker is enriched in serine/threonine, acidic residues (aspartate/glutamate), and structural residues (glycine/proline), providing additional layers of transcriptional regulation possibly through post-translational modification, electrostatic modulation, and/or condensate formation. We also examined six missense mutations in base-interacting residues, that are associated with neurodevelopmental disorders. Substitutions replacing bulky, positively charged arginine or lysine with smaller or hydrophobic residues likely reduce DNA-binding affinity and/or specificity, whereas substitutions between asparagine and lysine may alter base recognition preferences.

PubMed: 42232506
DOI: 10.64898/2026.05.01.721897

実験手法

X-RAY DIFFRACTION (2.81 Å)