N-terminal domain of polypyrimidine-tract binding protein is a dynamic folding platform for adaptive RNA recognition
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00598827" target="_blank" >RIV/68081707:_____/24:00598827 - isvavai.cz</a>
Result on the web
<a href="https://academic.oup.com/nar/article/52/17/10683/7740593" target="_blank" >https://academic.oup.com/nar/article/52/17/10683/7740593</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkae713" target="_blank" >10.1093/nar/gkae713</a>
Alternative languages
Result language
angličtina
Original language name
N-terminal domain of polypyrimidine-tract binding protein is a dynamic folding platform for adaptive RNA recognition
Original language description
The N-terminal RNA recognition motif domain (RRM1) of polypyrimidine tract binding protein (PTB) forms an additional C-terminal helix alpha 3, which docks to one edge of the beta-sheet upon binding to a stem-loop RNA containing a UCUUU pentaloop. Importantly, alpha 3 does not contact the RNA. The alpha 3 helix therefore represents an allosteric means to regulate the conformation of adjacent domains in PTB upon binding structured RNAs. Here we investigate the process of dynamic adaptation by stem-loop RNA and RRM1 using NMR and MD in order to obtain mechanistic insights on how this allostery is achieved. Relaxation data and NMR structure determination of the free protein show that alpha 3 is partially ordered and interacts with the domain transiently. Stem-loop RNA binding quenches fast time scale dynamics and alpha 3 becomes ordered, however microsecond dynamics at the protein-RNA interface is observed. MD shows how RRM1 binding to the stem-loop RNA is coupled to the stabilization of the C-terminal helix and helps to transduce differences in RNA loop sequence into changes in alpha 3 length and order. IRES assays of full length PTB and a mutant with altered dynamics in the alpha 3 region show that this dynamic allostery influences PTB function in cultured HEK293T cells.
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/GA23-05639S" target="_blank" >GA23-05639S: Molecular dynamics simulations of RNA: from static structures to molecular ensembles</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nucleic Acids Research
ISSN
0305-1048
e-ISSN
1362-4962
Volume of the periodical
52
Issue of the periodical within the volume
17
Country of publishing house
US - UNITED STATES
Number of pages
22
Pages from-to
10683-10704
UT code for WoS article
001297149500001
EID of the result in the Scopus database
2-s2.0-85204819720