Characterization of SARS-CoV-2 Nucleocapsid Protein Reveals Multiple Functional Consequences of the C-terminal Domain

Overview

Journal iScience

Publisher Cell Press

Date 2021 Jun 7

PMID 34095780

Citations 58

Authors

Chao Wu

Abraham J Qavi

Asmaa Hachim

Niloufar Kavian

Aidan R Cole

Austin B Moyle

Nicole D Wagner

Joyce Sweeney-Gibbons

Henry W Rohrs

Michael L Gross

J S Malik Peiris

Christopher F Basler

Christopher W Farnsworth

Sophie A Valkenburg

Gaya K Amarasinghe

Daisy W Leung

Affiliations

Soon will be listed here.

Abstract

Nucleocapsid (N) encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays key roles in the replication cycle and is a critical serological marker. Here, we characterize essential biochemical properties of N and describe the utility of these insights in serological studies. We define N domains important for oligomerization and RNA binding and show that N oligomerization provides a high-affinity RNA-binding platform. We also map the RNA-binding interface, showing protection in the N-terminal domain and linker region. In addition, phosphorylation causes reduction of RNA binding and redistribution of N from liquid droplets to loose coils, showing how N-RNA accessibility and assembly may be regulated by phosphorylation. Finally, we find that the C-terminal domain of N is the most immunogenic, based on antibody binding to patient samples. Together, we provide a biochemical description of SARS-CoV-2 N and highlight the value of using N domains as highly specific and sensitive diagnostic markers.

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