Residues flanking the ARK^me3T/S motif allow binding of diverse targets to the HP1 chromodomain: Insights from molecular dynamics simulations
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F21%3A00118823" target="_blank" >RIV/00216224:14310/21:00118823 - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/21:00542005
Result on the web
<a href="https://doi.org/10.1016/j.bbagen.2020.129771" target="_blank" >https://doi.org/10.1016/j.bbagen.2020.129771</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bbagen.2020.129771" target="_blank" >10.1016/j.bbagen.2020.129771</a>
Alternative languages
Result language
angličtina
Original language name
Residues flanking the ARK^me3T/S motif allow binding of diverse targets to the HP1 chromodomain: Insights from molecular dynamics simulations
Original language description
Background: The chromodomain (CD) of HP1 proteins is an established H3K9(me3) reader that also binds H1, EHMT2 and H3K23 lysine-methylated targets. Structural experiments have provided atomistic pictures of its recognition of the conserved ARK(me3)S/T motif, but structural dynamics' contribution to the recognition may have been masked by ensemble averaging. Methods: We acquired similar to 350 mu s of explicit solvent molecular dynamics (MD) simulations of the CD domain interacting with several peptides using the latest AMBER force fields. Results: The simulations reproduced the experimentally observed static binding patterns well but also revealed visible structural dynamics at the interfaces. While the buried K-0(me3) and A(-2) target residues are tightly bound, several flanking sidechains sample diverse sites on the CD surface. Different amino acid positions of the targets can substitute for each other by forming mutually replaceable interactions with CD, thereby explaining the lack of strict requirement for cationic H3 target residues at the -3 position. The Q(-4) residue of H3 targets further stabilizes the binding. The recognition pattern of the H3K23 ATK(me3)A motif, for which no structure is available, is predicted. Conclusions: The CD reads a longer target segment than previously thought, ranging from positions -7 to +3. The CD anionic clamp can be neutralized not only by the -3 and -1 residues, but also by -7, -6, -5 and +3 residues. General Significance: Structural dynamics, not immediately apparent from the structural data, contribute to molecular recognition between the HP1 CD domain and its targets. Mutual replaceability of target residues increases target sequence flexibility.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA18-07384S" target="_blank" >GA18-07384S: From conformation to biological functions of HP1 protein</a><br>
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
Biochimica et Biophysica Acta - General Subjects
ISSN
0304-4165
e-ISSN
1872-8006
Volume of the periodical
1865
Issue of the periodical within the volume
1
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
12
Pages from-to
1-12
UT code for WoS article
000594131800032
EID of the result in the Scopus database
2-s2.0-85094907445