[Figure: see text].
- MeSH
- adaptorové proteiny signální transdukční chemie metabolismus MeSH
- DNA vazebné proteiny chemie metabolismus MeSH
- elongace genetické transkripce * MeSH
- exprese genu MeSH
- interakční proteinové domény a motivy genetika MeSH
- lidé MeSH
- mapy interakcí proteinů MeSH
- molekulární modely MeSH
- mutace MeSH
- nádorové buněčné linie MeSH
- proteinové domény MeSH
- proteiny vázající RNA chemie genetika metabolismus MeSH
- RNA-polymerasa II chemie metabolismus MeSH
- transkripční elongační faktory chemie metabolismus MeSH
- transkripční faktory chemie genetika metabolismus MeSH
- vazba proteinů MeSH
- vnitřně neuspořádané proteiny chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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.
