Structure of an internal loop motif with three consecutive U•U mismatches from stem-loop 1 in the 3′-UTR of the SARS-CoV-2 genomic RNA

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00587348" target="_blank" >RIV/68081707:_____/24:00587348 - isvavai.cz</a>

Výsledek na webu

<a href="https://academic.oup.com/nar/article/52/11/6687/7680630?login=true" target="_blank" >https://academic.oup.com/nar/article/52/11/6687/7680630?login=true</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkae349" target="_blank" >10.1093/nar/gkae349</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structure of an internal loop motif with three consecutive U•U mismatches from stem-loop 1 in the 3′-UTR of the SARS-CoV-2 genomic RNA

Popis výsledku v původním jazyce

The single-stranded RNA genome of SARS-CoV-2 is highly structured. Numerous helical stem-loop structures interrupted by mismatch motifs are present in the functionally important 5 '- and 3 '-UTRs. These mismatches modulate local helical geometries and feature unusual arrays of hydrogen bonding donor and acceptor groups. However, their conformational and dynamical properties cannot be directly inferred from chemical probing and are difficult to predict theoretically. A mismatch motif (SL1-motif) consisting of three consecutive U center dot U base pairs is located in stem-loop 1 of the 3 '-UTR. We combined NMR-spectroscopy and MD-simulations to investigate its structure and dynamics. All three U center dot U base pairs feature two direct hydrogen bonds and are as stable as Watson-Crick A:U base pairs. Plasmodium falciparum 25S rRNA contains a triple U center dot U mismatch motif (Pf-motif) differing from SL1-motif only with respect to the orientation of the two closing base pairs. Interestingly, while the geometry of the outer two U center dot U mismatches was identical in both motifs the preferred orientation of the central U center dot U mismatch was different. MD simulations and potassium ion titrations revealed that the potassium ion-binding mode to the major groove is connected to the different preferred geometries of the central base pair in the two motifs.

Název v anglickém jazyce

Structure of an internal loop motif with three consecutive U•U mismatches from stem-loop 1 in the 3′-UTR of the SARS-CoV-2 genomic RNA

Popis výsledku anglicky

The single-stranded RNA genome of SARS-CoV-2 is highly structured. Numerous helical stem-loop structures interrupted by mismatch motifs are present in the functionally important 5 '- and 3 '-UTRs. These mismatches modulate local helical geometries and feature unusual arrays of hydrogen bonding donor and acceptor groups. However, their conformational and dynamical properties cannot be directly inferred from chemical probing and are difficult to predict theoretically. A mismatch motif (SL1-motif) consisting of three consecutive U center dot U base pairs is located in stem-loop 1 of the 3 '-UTR. We combined NMR-spectroscopy and MD-simulations to investigate its structure and dynamics. All three U center dot U base pairs feature two direct hydrogen bonds and are as stable as Watson-Crick A:U base pairs. Plasmodium falciparum 25S rRNA contains a triple U center dot U mismatch motif (Pf-motif) differing from SL1-motif only with respect to the orientation of the two closing base pairs. Interestingly, while the geometry of the outer two U center dot U mismatches was identical in both motifs the preferred orientation of the central U center dot U mismatch was different. MD simulations and potassium ion titrations revealed that the potassium ion-binding mode to the major groove is connected to the different preferred geometries of the central base pair in the two motifs.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA23-05639S" target="_blank" >GA23-05639S: Molekulové simulace RNA: od statických struktur k molekulárním souborům</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

1362-4962

Svazek periodika

52

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

20

Strana od-do

6687-6706

Kód UT WoS článku

001230005600001

EID výsledku v databázi Scopus

2-s2.0-85196836622