Universal two-point interaction of mediator KIX with 9aaTAD activation domains
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00075355" target="_blank" >RIV/65269705:_____/21:00075355 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/21:00120140
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1002/jcb.30075" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/jcb.30075</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/jcb.30075" target="_blank" >10.1002/jcb.30075</a>
Alternative languages
Result language
angličtina
Original language name
Universal two-point interaction of mediator KIX with 9aaTAD activation domains
Original language description
The nine-amino-acid activation domain (9aaTAD) is defined by a short amino acid pattern including two hydrophobic regions (positions p3-4 and p6-7). The KIX domain of mediator transcription CBP interacts with the 9aaTAD domains of transcription factors MLL, E2A, NF-kB, and p53. In this study, we analyzed the 9aaTADs-KIX interactions by nuclear magnetic resonance. The positions of three KIX helixes alpha 1-alpha 2-alpha 3 are influenced by sterically-associated hydrophobic I611, L628, and I660 residues that are exposed to solvent. The positions of two rigid KIX helixes alpha 1 and alpha 2 generate conditions for structural folding in the flexible KIX-L12-G2 regions localized between them. The three KIX I611, L628, and I660 residues interact with two 9aaTAD hydrophobic residues in positions p3 and p4 and together build a hydrophobic core of five residues (5R). Numerous residues in 9aaTAD position p3 and p4 could provide this interaction. Following binding of the 9aaTAD to KIX, the hydrophobic I611, L628, and I660 residues are no longer exposed to solvent and their position changes inside the hydrophobic core together with position of KIX alpha 1-alpha 2-alpha 3 helixes. The new positions of the KIX helixes alpha 1 and alpha 2 allow the KIX-L12-G2 enhanced formation. The second hydrophobic region of the 9aaTAD (positions p6 and p7) provides strong binding with the KIX-L12-G2 region. Similarly, multiple residues in 9aaTAD position p6 and p7 could provide this interaction. In conclusion, both 9aaTAD regions p3, p4 and p6, p7 provide co-operative and highly universal binding to mediator KIX. The hydrophobic core 5R formation allows new positions of the rigid KIX alpha-helixes and enables the enhanced formation of the KIX-L12-G2 region. This contributes to free energy and is the key for the KIX-9aaTAD binding. Therefore, the 9aaTAD-KIX interactions do not operate under the rigid key-and-lock mechanism what explains the 9aaTAD natural variability.
Czech name
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Czech description
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Classification
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
30200 - Clinical medicine
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Cellular Biochemistry
ISSN
0730-2312
e-ISSN
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Volume of the periodical
122
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
1544-1555
UT code for WoS article
000669605600001
EID of the result in the Scopus database
2-s2.0-85109188946