How Binding Site Flexibility Promotes RNA Scanning by TbRGG2 RRM: A Molecular Dynamics Simulation Study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F25%3A00605575" target="_blank" >RIV/68081707:_____/25:00605575 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/25:00140510
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jcim.4c01954" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jcim.4c01954</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jcim.4c01954" target="_blank" >10.1021/acs.jcim.4c01954</a>
Alternative languages
Result language
angličtina
Original language name
How Binding Site Flexibility Promotes RNA Scanning by TbRGG2 RRM: A Molecular Dynamics Simulation Study
Original language description
RNA recognition motifs (RRMs) are a key class of proteins that primarily bind single-stranded RNAs. In this study, we applied standard atomistic molecular dynamics simulations to obtain insights into the intricate binding dynamics between uridine-rich RNAs and TbRGG2 RRM using the recently developed OL3-Stafix AMBER force field, which improves the description of single-stranded RNA molecules. Complementing structural experiments that unveil a primary binding mode with a single uridine bound, our simulations uncover two supplementary binding modes in which adjacent nucleotides encroach upon the binding pocket. This leads to a unique molecular mechanism through which the TbRGG2 RRM is capable of rapidly transitioning the U-rich sequence. In contrast, the presence of non-native cytidines induces stalling and destabilization of the complex. By leveraging extensive equilibrium dynamics and a large variety of binding states, TbRGG2 RRM effectively expedites diffusion along the RNA substrate while ensuring robust selectivity for U-rich sequences despite featuring a solitary binding pocket. We further substantiate our description of the complex dynamics by simulating the fully spontaneous association process of U-rich sequences to the TbRGG2 RRM. Our study highlights the critical role of dynamics and auxiliary binding states in interface dynamics employed by RNA-binding proteins, which is not readily apparent in traditional structural studies but could represent a general type of binding strategy employed by many RNA-binding proteins.
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
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
Others
Publication year
2025
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 Chemical Information and Modeling
ISSN
1549-9596
e-ISSN
1549-960X
Volume of the periodical
65
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
896-907
UT code for WoS article
001396998800001
EID of the result in the Scopus database
2-s2.0-85215846781