MD simulations reveal the basis for dynamic assembly of Hfq-RNA complexes
Identifikátory výsledku
Kód výsledku v 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>
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
MD simulations reveal the basis for dynamic assembly of Hfq-RNA complexes
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
MD simulations reveal the basis for dynamic assembly of Hfq-RNA complexes
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
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OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
<a href="/cs/project/GA20-16554S" target="_blank" >GA20-16554S: Molekulové modelování RNA molekul a jejích komplexů: Úloha strukturní dynamiky</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Biological Chemistry
ISSN
0021-9258
e-ISSN
1083-351X
Svazek periodika
296
Číslo periodika v rámci svazku
JAN-JUN 2021
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
15
Strana od-do
100656
Kód UT WoS článku
000672866400627
EID výsledku v databázi Scopus
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