A distinct ssDNA/RNA binding interface in the Nsp9 protein from SARS-CoV-2

Serene El-Kamand; Mar-Dean Du Plessis; Natasha Breen; Lexie Johnson; Samuel Beard; Ann H. Kwan; Derek J. Richard; Liza Cubeddu; Roland Gamsjaeger

doi:10.1002/prot.26205

A distinct ssDNA/RNA binding interface in the Nsp9 protein from SARS-CoV-2

Serene El-Kamand, Mar-Dean Du Plessis, Natasha Breen, Lexie Johnson, Samuel Beard, Ann H. Kwan, Derek J. Richard, Liza Cubeddu, Roland Gamsjaeger

Western Sydney University

Research output: Contribution to journal › Article › peer-review

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel, highly infectious RNA virus that belongs to the coronavirus family. Replication of the viral genome is a fundamental step in the virus life cycle and SARS-CoV-2 non-structural protein 9 (Nsp9) is shown to be essential for virus replication through its ability to bind RNA in the closely related SARS-CoV-1 strain. Two recent studies revealing the three-dimensional structure of Nsp9 from SARS-CoV-2 have demonstrated a high degree of similarity between Nsp9 proteins within the coronavirus family. However, the binding affinity to RNA is very low which, until now, has prevented the determination of the structural details of this interaction. In this study, we have utilized nuclear magnetic resonance spectroscopy (NMR) in combination with surface biolayer interferometry (BLI) to reveal a distinct binding interface for both ssDNA and RNA that is different to the one proposed in the recently solved SARS-CoV-2 replication and transcription complex (RTC) structure. Based on these data, we have proposed a structural model of a Nsp9-RNA complex, shedding light on the molecular details of these important interactions.

Original language	English
Pages (from-to)	176-185
Number of pages	10
Journal	Proteins
Volume	90
Issue number	1
DOIs	https://doi.org/10.1002/prot.26205
Publication status	Published - 2022

Open Access - Access Right Statement

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2021 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.

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10.1002/prot.26205

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@article{562034c0e09b40609b13cb49d71ac1d0,

title = "A distinct ssDNA/RNA binding interface in the Nsp9 protein from SARS-CoV-2",

abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel, highly infectious RNA virus that belongs to the coronavirus family. Replication of the viral genome is a fundamental step in the virus life cycle and SARS-CoV-2 non-structural protein 9 (Nsp9) is shown to be essential for virus replication through its ability to bind RNA in the closely related SARS-CoV-1 strain. Two recent studies revealing the three-dimensional structure of Nsp9 from SARS-CoV-2 have demonstrated a high degree of similarity between Nsp9 proteins within the coronavirus family. However, the binding affinity to RNA is very low which, until now, has prevented the determination of the structural details of this interaction. In this study, we have utilized nuclear magnetic resonance spectroscopy (NMR) in combination with surface biolayer interferometry (BLI) to reveal a distinct binding interface for both ssDNA and RNA that is different to the one proposed in the recently solved SARS-CoV-2 replication and transcription complex (RTC) structure. Based on these data, we have proposed a structural model of a Nsp9-RNA complex, shedding light on the molecular details of these important interactions.",

author = "Serene El-Kamand and {Du Plessis}, Mar-Dean and Natasha Breen and Lexie Johnson and Samuel Beard and Kwan, {Ann H.} and Richard, {Derek J.} and Liza Cubeddu and Roland Gamsjaeger",

year = "2022",

doi = "10.1002/prot.26205",

language = "English",

volume = "90",

pages = "176--185",

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T1 - A distinct ssDNA/RNA binding interface in the Nsp9 protein from SARS-CoV-2

AU - El-Kamand, Serene

AU - Du Plessis, Mar-Dean

AU - Breen, Natasha

AU - Johnson, Lexie

AU - Beard, Samuel

AU - Kwan, Ann H.

AU - Richard, Derek J.

AU - Cubeddu, Liza

AU - Gamsjaeger, Roland

PY - 2022

Y1 - 2022

N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel, highly infectious RNA virus that belongs to the coronavirus family. Replication of the viral genome is a fundamental step in the virus life cycle and SARS-CoV-2 non-structural protein 9 (Nsp9) is shown to be essential for virus replication through its ability to bind RNA in the closely related SARS-CoV-1 strain. Two recent studies revealing the three-dimensional structure of Nsp9 from SARS-CoV-2 have demonstrated a high degree of similarity between Nsp9 proteins within the coronavirus family. However, the binding affinity to RNA is very low which, until now, has prevented the determination of the structural details of this interaction. In this study, we have utilized nuclear magnetic resonance spectroscopy (NMR) in combination with surface biolayer interferometry (BLI) to reveal a distinct binding interface for both ssDNA and RNA that is different to the one proposed in the recently solved SARS-CoV-2 replication and transcription complex (RTC) structure. Based on these data, we have proposed a structural model of a Nsp9-RNA complex, shedding light on the molecular details of these important interactions.

AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel, highly infectious RNA virus that belongs to the coronavirus family. Replication of the viral genome is a fundamental step in the virus life cycle and SARS-CoV-2 non-structural protein 9 (Nsp9) is shown to be essential for virus replication through its ability to bind RNA in the closely related SARS-CoV-1 strain. Two recent studies revealing the three-dimensional structure of Nsp9 from SARS-CoV-2 have demonstrated a high degree of similarity between Nsp9 proteins within the coronavirus family. However, the binding affinity to RNA is very low which, until now, has prevented the determination of the structural details of this interaction. In this study, we have utilized nuclear magnetic resonance spectroscopy (NMR) in combination with surface biolayer interferometry (BLI) to reveal a distinct binding interface for both ssDNA and RNA that is different to the one proposed in the recently solved SARS-CoV-2 replication and transcription complex (RTC) structure. Based on these data, we have proposed a structural model of a Nsp9-RNA complex, shedding light on the molecular details of these important interactions.

UR - http://hdl.handle.net/1959.7/uws:60680

U2 - 10.1002/prot.26205

DO - 10.1002/prot.26205

M3 - Article

SN - 0887-3585

VL - 90

SP - 176

EP - 185

JO - Proteins

JF - Proteins

IS - 1

ER -

A distinct ssDNA/RNA binding interface in the Nsp9 protein from SARS-CoV-2

Abstract

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