 |
PDBsum entry 6tvm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription
|
PDB id
|
|
|
|
6tvm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Transcription
|
|
|
Title:
|
|
Ledgf/p75 dimer (residues 345-467)
|
|
Structure:
|
|
Pc4 and sfrs1-interacting protein. Chain: a, b. Synonym: cll-associated antigen kw-7,dense fine speckles 70 kda protein,dfs 70,lens epithelium-derived growth factor,transcriptional coactivator p75/p52. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: psip1, dfs70, ledgf, psip2. Expressed in: escherichia coli. Expression_system_taxid: 562
|
|
NMR struc:
|
|
30 models
|
|
|
Authors:
|
|
V.Lux,V.Veverka
|
|
Key ref:
|
|
V.Lux
et al.
(2020).
Molecular Mechanism of LEDGF/p75 Dimerization.
Structure,
28,
1288.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
10-Jan-20
|
Release date:
|
09-Sep-20
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
O75475
(PSIP1_HUMAN) -
PC4 and SFRS1-interacting protein from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
530 a.a.
128 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
|
*
PDB and UniProt seqs differ
at 5 residue positions (black
crosses)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Structure
28:1288
(2020)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Molecular Mechanism of LEDGF/p75 Dimerization.
|
|
V.Lux,
T.Brouns,
K.Čermáková,
P.Srb,
M.Fábry,
M.Mádlíková,
M.Hořejší,
Z.Kukačka,
P.Novák,
M.Kugler,
J.Brynda,
J.DeRijck,
F.Christ,
Z.Debyser,
V.Veverka.
|
|
|
|
|
| |
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.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
