Force-dependent stimulation of RNA unwinding by SARS-CoV-2 nsp13 helicase.
Biophys J
; 120(6): 1020-1030, 2021 03 16.
Article
in English
| MEDLINE | ID: covidwho-987186
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The superfamily 1 helicase nonstructural protein 13 (nsp13) is required for SARS-CoV-2 replication. The mechanism and regulation of nsp13 has not been explored at the single-molecule level. Specifically, force-dependent unwinding experiments have yet to be performed for any coronavirus helicase. Here, using optical tweezers, we find that nsp13 unwinding frequency, processivity, and velocity increase substantially when a destabilizing force is applied to the RNA substrate. These results, along with bulk assays, depict nsp13 as an intrinsically weak helicase that can be activated >50-fold by piconewton forces. Such force-dependent behavior contrasts the known behavior of other viral monomeric helicases, such as hepatitis C virus NS3, and instead draws stronger parallels to ring-shaped helicases. Our findings suggest that mechanoregulation, which may be provided by a directly bound RNA-dependent RNA polymerase, enables on-demand helicase activity on the relevant polynucleotide substrate during viral replication.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
DNA, Viral
/
RNA, Viral
/
Viral Nonstructural Proteins
/
RNA Helicases
/
SARS-CoV-2
/
Methyltransferases
Language:
English
Journal:
Biophys J
Year:
2021
Document Type:
Article
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