9BVD

Crystal structure of SRY HMG box bound to DNA

9BVD の概要

• エントリーDOI: 10.2210/pdb9bvd/pdb
• 分子名称: Sex-determining region Y protein, DNA (5'-D(*CP*AP*CP*TP*AP*GP*CP*AP*TP*TP*GP*TP*TP*TP*GP*GP*G)-3'), DNA (5'-D(*GP*CP*CP*CP*AP*AP*AP*CP*AP*AP*TP*GP*CP*TP*AP*GP*TP*G)-3'), ... (5 entities in total)
• 機能のキーワード: dna-complex, transcription factor, sex-determination, sry, 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: 9
• 化学式量合計: 62175.22

構造登録者

Georgiadis, M.M. (登録日: 2024-05-20, 公開日: 2024-09-25, 最終更新日: 2024-10-09)

主引用文献

Racca, J.D.,Chen, Y.S.,Brabender, A.R.,Battistin, U.,Weiss, M.A.,Georgiadis, M.M.
Role of nucleobase-specific interactions in the binding and bending of DNA by human male sex determination factor SRY.
J.Biol.Chem., 300:107683-107683, 2024

PubMed Abstract: Y-chromosome-encoded master transcription factor SRY functions in the embryogenesis of therian mammals to initiate male development. Through interactions of its conserved high-mobility group box within a widened DNA minor groove, SRY and related Sox factors induce sharp bends at specific DNA target sites. Here, we present the crystal structure of the SRY high-mobility group domain bound to a DNA site containing consensus element 5'-ATTGTT. The structure contains three complexes in the asymmetric unit; in each complex, SRY forms 10 hydrogen bonds with minor-groove base atoms in 5'-CATTGT/ACAATG-3', shifting the recognition sequence by one base pair (italics). These nucleobase interactions involve conserved residues Arg7, Asn10, and Tyr74 on one side of intercalated Ile13 (the cantilever) and Arg20, Asn32, and Ser36 on the other. Unlike the less-bent NMR structure, DNA bend angles (69-84°) of the distinct box-DNA complexes are similar to those observed in homologous Sox domain-DNA structures. Electrophoretic studies indicate that respective substitutions of Asn32, Ser36, or Tyr74 by Ala exhibit slightly attenuated specific DNA-binding affinity and bend angles (70-73°) relative to WT (79°). By contrast, respective substitutions of Arg7, Asn10, or Arg20 by Ala markedly impaired DNA-binding affinity in association with much smaller DNA bend angles (53-65°). In a rodent cell-based model of the embryonic gonadal ridge, full-length SRY variants bearing these respective Ala substitutions exhibited significantly decreased transcriptional activation of SRY's principal target gene (Sox9). Together, our findings suggest that nucleobase-specific hydrogen bonds by SRY are critical for specific DNA binding, bending, and transcriptional activation.

PubMed: 39168182
DOI: 10.1016/j.jbc.2024.107683

実験手法

X-RAY DIFFRACTION (2.48 Å)