6TYD

Structure of human LDB1 in complex with SSBP2

6TYD の概要

• エントリーDOI: 10.2210/pdb6tyd/pdb
• 分子名称: LIM domain-binding protein 1, Single-stranded DNA-binding protein 2 (2 entities in total)
• 機能のキーワード: ldb1, ssbp2, chils, transcription
• 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: 49707.73

構造登録者

Wang, H.,Wang, Z.,Xu, W. (登録日: 2019-08-08, 公開日: 2020-01-01, 最終更新日: 2024-10-23)

主引用文献

Wang, H.,Kim, J.,Wang, Z.,Yan, X.X.,Dean, A.,Xu, W.
Crystal structure of human LDB1 in complex with SSBP2.
Proc.Natl.Acad.Sci.USA, 117:1042-1048, 2020

PubMed Abstract: The Lim domain binding proteins (LDB1 and LDB2 in human and Chip in ) play critical roles in cell fate decisions through partnership with multiple Lim-homeobox and Lim-only proteins in diverse developmental systems including cardiogenesis, neurogenesis, and hematopoiesis. In mammalian erythroid cells, LDB1 dimerization supports long-range connections between enhancers and genes involved in erythropoiesis, including the β-globin genes. Single-stranded DNA binding proteins (SSBPs) interact specifically with the LDB/Chip conserved domain (LCCD) of LDB proteins and stabilize LDBs by preventing their proteasomal degradation, thus promoting their functions in gene regulation. The structural basis for LDB1 self-interaction and interface with SSBPs is unclear. Here we report a crystal structure of the human LDB1/SSBP2 complex at 2.8-Å resolution. The LDB1 dimerization domain (DD) contains an N-terminal nuclear transport factor 2 (NTF2)-like subdomain and a small helix 4-helix 5 subdomain, which together form the LDB1 dimerization interface. The 2 LCCDs in the symmetric LDB1 dimer flank the core DDs, with each LCCD forming extensive interactions with an SSBP2 dimer. The conserved linker between LDB1 DD and LCCD covers a potential ligand-binding pocket of the LDB1 NTF2-like subdomain and may serve as a regulatory site for LDB1 structure and function. Our structural and biochemical data provide a much-anticipated structural basis for understanding how LDB1 and the LDB1/SSBP interactions form the structural core of diverse complexes mediating cell choice decisions and long-range enhancer-promoter interactions.

PubMed: 31892537
DOI: 10.1073/pnas.1914181117

実験手法

X-RAY DIFFRACTION (2.803 Å)