6TVM
LEDGF/p75 dimer (residues 345-467)
Summary for 6TVM
| Entry DOI | 10.2210/pdb6tvm/pdb |
| NMR Information | BMRB: 34475 |
| Descriptor | PC4 and SFRS1-interacting protein (1 entity in total) |
| Functional Keywords | epigenetic reader, integrase-binding domain, domain-swapped dimer, transcription |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 29289.71 |
| Authors | Lux, V.,Veverka, V. (deposition date: 2020-01-10, release date: 2020-09-09, Last modification date: 2024-06-19) |
| Primary citation | 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 Cited by 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: 32946742DOI: 10.1016/j.str.2020.08.012 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
