2023
Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106
KOUBA, Tomas, Anna DUBANKOVA, Petra DRNCOVA, Elisa DONATI, Pietro VIDOSSICH et. al.Základní údaje
Originální název
Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106
Autoři
KOUBA, Tomas, Anna DUBANKOVA, Petra DRNCOVA, Elisa DONATI, Pietro VIDOSSICH, Valentina SPERANZINI, Alex PFLUG, Johanna HUCHTING, Chris MEIER, De Vivo MARCO a Stephen CUSACK (garant)
Vydání
Cell Reports, CAMBRIDGE, Cell Press, 2023, 2211-1247
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10601 Cell biology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 8.800 v roce 2022
Kód RIV
RIV/00216224:90242/23:00133755
Organizační jednotka
CIISB III
UT WoS
000964718900001
Klíčová slova anglicky
T-705 FAVIPIRAVIR; TRANSCRIPTION; RNA polymerase; REPLICATION; INFECTIONS; CryoEM; pyr-azinecarboxamide base analogs
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 11. 4. 2024 23:16, Mgr. Michal Petr
Anotace
V originále
The antiviral pseudo-base T705 and its de-fluoro analog T1106 mimic adenine or guanine and can be compet-itively incorporated into nascent RNA by viral RNA-dependent RNA polymerases. Although dispersed, single pseudo-base incorporation is mutagenic, consecutive incorporation causes polymerase stalling and chain termination. Using a template encoding single and then consecutive T1106 incorporation four nucleotides later, we obtained a cryogenic electron microscopy structure of stalled influenza A/H7N9 polymerase. This shows that the entire product-template duplex backtracks by 5 nt, bringing the singly incorporated T1106 to the +1 position, where it forms an unexpected T1106:U wobble base pair. Similar structures show that influ-enza B polymerase also backtracks after consecutive T1106 incorporation, regardless of whether prior single incorporation has occurred. These results give insight into the unusual mechanism of chain termination by pyr-azinecarboxamide base analogs. Consecutive incorporation destabilizes the proximal end of the product -template duplex, promoting irreversible backtracking to a more energetically favorable overall configuration.
Návaznosti
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