Molecular Mechanism of LEDGF/p75 Dimerization

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00533337" target="_blank" >RIV/61388963:_____/20:00533337 - isvavai.cz</a>
Alternative codes found
RIV/61388971:_____/20:00533337 RIV/68378050:_____/20:00539172 RIV/00216208:11310/20:10422204
Result on the web
<a href="https://doi.org/10.1016/j.str.2020.08.012" target="_blank" >https://doi.org/10.1016/j.str.2020.08.012</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.str.2020.08.012" target="_blank" >10.1016/j.str.2020.08.012</a>

Result language
angličtina
Original language name
Molecular Mechanism of LEDGF/p75 Dimerization
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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