MD simulations reveal the basis for dynamic assembly of Hfq-RNA complexes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00553643" target="_blank" >RIV/68081707:_____/21:00553643 - isvavai.cz</a>
Result on the web
<a href="https://www.jbc.org/action/showPdf?pii=S0021-9258%2821%2900443-9" target="_blank" >https://www.jbc.org/action/showPdf?pii=S0021-9258%2821%2900443-9</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jbc.2021.100656" target="_blank" >10.1016/j.jbc.2021.100656</a>
Alternative languages
Result language
angličtina
Original language name
MD simulations reveal the basis for dynamic assembly of Hfq-RNA complexes
Original language description
The conserved protein Hfq is a key factor in the RNA-mediated control of gene expression in most known bacteria. The transient intermediates Hfq forms with RNA support intricate and robust regulatory networks. In Pseudomonas, Hfq recognizes repeats of adenine-purine-any nucleotide (ARN) in target mRNAs via its distal binding side, and together with the catabolite repression control (Crc) protein, assembles into a translation-repression complex. Earlier experiments yielded static, ensemble-averaged structures of the complex, but details of its interface dynamics and assembly pathway remained elusive. Using explicit solvent atomistic molecular dynamics simulations, we modeled the extensive dynamics of the Hfq-RNA interface and found implications for the assembly of the complex. We predict that syn/anti flips of the adenine nucleotides in each ARN repeat contribute to a dynamic recognition mechanism between the Hfq distal side and mRNA targets. We identify a previously unknown binding pocket that can accept any nucleotide and propose that it may serve as a 'status quo' staging point, providing nonspecific binding affinity, until Crc engages the Hfq-RNA binary complex. The dynamical components of the Hfq-RNA recognition can speed up screening of the pool of the surrounding RNAs, participate in rapid accommodation of the RNA on the protein surface, and facilitate competition among different RNAs. The register of Crc in the ternary assembly could be defined by the recognition of a guanine-specific base-phosphate interaction between the first and last ARN repeats of the bound RNA. This dynamic substrate recognition provides structural rationale for the stepwise assembly of multicomponent ribonucleoprotein complexes nucleated by Hfq-RNA binding.
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/GA20-16554S" target="_blank" >GA20-16554S: Molecular modeling of RNA molecules and their complexes: the role of structural dynamics</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
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 Biological Chemistry
ISSN
0021-9258
e-ISSN
1083-351X
Volume of the periodical
296
Issue of the periodical within the volume
JAN-JUN 2021
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
100656
UT code for WoS article
000672866400627
EID of the result in the Scopus database
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