6TVM

LEDGF/p75 dimer (residues 345-467)

6TVM の概要

• エントリーDOI: 10.2210/pdb6tvm/pdb
• NMR情報: BMRB: 34475
• 分子名称: PC4 and SFRS1-interacting protein (1 entity in total)
• 機能のキーワード: epigenetic reader, integrase-binding domain, domain-swapped dimer, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29289.71

構造登録者

Lux, V.,Veverka, V. (登録日: 2020-01-10, 公開日: 2020-09-09, 最終更新日: 2024-06-19)

主引用文献

Lux, V.,Brouns, T.,Cermakova, K.,Srb, P.,Fabry, M.,Madlikova, M.,Horejsi, M.,Kukacka, Z.,Novak, P.,Kugler, M.,Brynda, J.,DeRijck, J.,Christ, F.,Debyser, Z.,Veverka, V.
Molecular Mechanism of LEDGF/p75 Dimerization.
Structure, 28:1288-1299.e7, 2020

PubMed Abstract: Dimerization of many eukaryotic transcription regulatory factors is critical for their function. Regulatory role of an epigenetic reader lens epithelium-derived growth factor/p75 (LEDGF/p75) requires at least two copies of this protein to overcome the nucleosome-induced barrier to transcription elongation. Moreover, various LEDGF/p75 binding partners are enriched for dimeric features, further underscoring the functional regulatory role of LEDGF/p75 dimerization. Here, we dissected the minimal dimerization region in the C-terminal part of LEDGF/p75 and, using paramagnetic NMR spectroscopy, identified the key molecular contacts that helped to refine the solution structure of the dimer. The LEDGF/p75 dimeric assembly is stabilized by domain swapping within the integrase binding domain and additional electrostatic "stapling" of the negatively charged α helix formed in the intrinsically disordered C-terminal region. We validated the dimerization mechanism using structure-inspired dimerization defective LEDGF/p75 variants and chemical crosslinking coupled to mass spectrometry. We also show how dimerization might affect the LEDGF/p75 interactome.

PubMed: 32946742
DOI: 10.1016/j.str.2020.08.012

実験手法

SOLUTION NMR