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PDBsum entry 6tvm
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Transcription
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PDB id
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6tvm
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References listed in PDB file
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Key reference
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Title
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Molecular mechanism of ledgf/p75 dimerization.
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Authors
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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.
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Ref.
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Structure, 2020,
28,
1288.
[DOI no: ]
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PubMed id
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Abstract
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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.
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