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Unwinding of a DNA replication fork by a hexameric viral helicase

DOI: 10.1038/s41467-021-25843-6 DOI Help

Authors: Abid Javed (Birkbeck College) , Balazs Major (University of Sheffield) , Jonathan A. Stead (University of Sheffield) , Cyril M. Sanders (University of Sheffield) , Elena V. Orlova (Birkbeck College)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 12

State: Published (Approved)
Published: September 2021
Diamond Proposal Number(s): 14704

Open Access Open Access

Abstract: Hexameric helicases are motor proteins that unwind double-stranded DNA (dsDNA) during DNA replication but how they are optimised for strand separation is unclear. Here we present the cryo-EM structure of the full-length E1 helicase from papillomavirus, revealing all arms of a bound DNA replication fork and their interactions with the helicase. The replication fork junction is located at the entrance to the helicase collar ring, that sits above the AAA + motor assembly. dsDNA is escorted to and the 5´ single-stranded DNA (ssDNA) away from the unwinding point by the E1 dsDNA origin binding domains. The 3´ ssDNA interacts with six spirally-arranged β-hairpins and their cyclical top-to-bottom movement pulls the ssDNA through the helicase. Pulling of the RF against the collar ring separates the base-pairs, while modelling of the conformational cycle suggest an accompanying movement of the collar ring has an auxiliary role, helping to make efficient use of ATP in duplex unwinding.

Journal Keywords: DNA replication; Electron microscopy; Origin selection; Structural biology

Diamond Keywords: Viruses

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 27/09/2021 10:33

Documents:
s41467-021-25843-6.pdf

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Infectious Diseases Pathogens Structural biology

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)