SARS-CoV-2 Nsp8 N-terminal Domain Folds Autonomously and Binds DsRNA

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2023 Sep 4

PMID 37665006

Authors

Miguel A Trevino

David Pantoja-Uceda

Douglas V Laurents

Miguel Mompean

Affiliations

Soon will be listed here.

Abstract

The SARS-CoV-2 Nsp8 protein is a critical component of the RNA replicase, as its N-terminal domain (NTD) anchors Nsp12, the RNA, and Nsp13. Whereas its C-terminal domain (CTD) structure is well resolved, there is an open debate regarding the conformation adopted by the NTD as it is predicted as disordered but found in a variety of complex-dependent conformations or missing from many other structures. Using NMR spectroscopy, we show that the SARS CoV-2 Nsp8 NTD features both well folded secondary structure and disordered segments. Our results suggest that while part of this domain corresponding to two long α-helices forms autonomously, the folding of other segments would require interaction with other replicase components. When isolated, the α-helix population progressively declines towards the C-termini but surprisingly binds dsRNA while preserving structural disorder.

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