Abstract

The newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global human health crisis. The CoV nucleocapsid (N) protein plays essential roles both in the viral genomic RNA packaging and the regulation of host cellular machinery. Here, to contribute to the structural information of the N protein, we describe the 2.0 Å crystal structure of the SARS-CoV-2 N protein C-terminal domain (N-CTD). The structure indicates an extensive interaction dimer in a domain-swapped manner. The interface of this dimer was first thoroughly illustrated. Also, the SARS-CoV-2 N-CTD dimerization form was verified in solution using size-exclusion chromatography. Based on the structural comparison of the N-CTDs from alpha-, beta-, and gamma-CoVs, we demonstrate the common and specific characteristics of the SARS-CoV-2 N-CTD. Furthermore, we provide evidence that the SARS-CoV-2 N-CTD possesses the binding ability to single-stranded RNA, single-stranded DNA as well as double-stranded DNA in vitro. In conclusion, this study could potentially accelerate research to understand the complete biological functions of the new CoV N protein.

Highlights

  • Over the past two decades, the emergence of novel human coronaviruses has caused continuous threats to the public health systems worldwide

  • We determined the crystal structure of SARS-CoV-2 N protein C-terminal domain (N-C-terminal domain (CTD)) at a resolution of 2.0 Å, and we report the interactions of the N-CTD homo-dimer in strong detail

  • Overall structure of the C-terminal domain of SARS-CoV-2 N protein (N-CTD) We designed a SARS-CoV-2 (GenBank: MN908947, [2]) N-CTD construct containing the residues from Lys248 to Pro364 of the N protein (Fig. 1a) and determined the three-dimensional structure of the corresponding region at 2.0 Å

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Summary

Introduction

Over the past two decades, the emergence of novel human coronaviruses has caused continuous threats to the public health systems worldwide. Severe acute respiratory syndrome coronavirus (SARS-CoV) infected more than 8000 people with ~ 10% fatality rate during the global outbreak of 2002/2003 [1]. Ten years later, another highly pathogenic agent, the Middle-East respiratory syndrome coronavirus (MERS-CoV) appeared in the Arabian Peninsula and currently infected approximately 2500 cases with a ~ 35% mortality rate (www.who.int). At the end of 2019, a new coronavirus (CoV), SARS-CoV-2 ( named 2019-nCoV) was identified (GenBank: MN908947, [2]). This new CoV could cause the so-called coronavirus disease 2019 (COVID-19). No efficient vaccine or treatment is available so far

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