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H-1, C-13 and N-15 resonance assignment of the SARS-CoV-2 full-length nsp1 protein and its mutants reveals its unique secondary structure features in solution

Agback, Tatiana and Dominguez, Francisco and Frolov, Ilya and Frolova, Elena I. and Agback, Peter (2021). H-1, C-13 and N-15 resonance assignment of the SARS-CoV-2 full-length nsp1 protein and its mutants reveals its unique secondary structure features in solution. PLoS ONE. 16 :12 , e0251834
[Research article]

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Abstract

Structural characterization of the SARS-CoV-2 full length nsp1 protein will be an essential tool for developing new target-directed antiviral drugs against SARS-CoV-2 and for further understanding of intra- and intermolecular interactions of this protein. As a first step in the NMR studies of the protein, we report the H-1, C-13 and N-15 resonance backbone assignment as well as the C beta of the apo form of the full-lengthSARS-CoV-2 nsp1 including the folded domain together with the flaking N- and C- terminal intrinsically disordered fragments. The 19.8 kD protein was characterized by high-resolution NMR. Validation of assignment have been done by using two different mutants, H81P and K129E/D48E as well as by amino acid specific experiments. According to the obtained assignment, the secondary structure of the folded domain in solution was almost identical to its previously published X-ray structure as well as another published secondary structure obtained by NMR, but some discrepancies have been detected. In the solution SARS-CoV-2 nsp1 exhibited disordered, flexible N- and C-termini with different dynamic characteristics. The short peptide in the beginning of the disordered C-terminal domain adopted two different conformations distinguishable on the NMR time scale. We propose that the disordered and folded nsp1 domains are not fully independent units but are rather involved in intramolecular interactions. Studies of the structure and dynamics of the SARS-CoV-2 mutant in solution are on-going and will provide important insights into the molecular mechanisms underlying these interactions.

Authors/Creators:Agback, Tatiana and Dominguez, Francisco and Frolov, Ilya and Frolova, Elena I. and Agback, Peter
Title:H-1, C-13 and N-15 resonance assignment of the SARS-CoV-2 full-length nsp1 protein and its mutants reveals its unique secondary structure features in solution
Series Name/Journal:PLoS ONE
Year of publishing :2021
Volume:16
Number:12
Article number:e0251834
Number of Pages:16
Publisher:PUBLIC LIBRARY SCIENCE
ISSN:1932-6203
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 304 Medical Biotechnology > Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
URN:NBN:urn:nbn:se:slu:epsilon-p-116325
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-116325
Additional ID:
Type of IDID
DOI10.1371/journal.pone.0251834
Web of Science (WoS)000753617500001
ID Code:27426
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Molecular Sciences
Deposited By: SLUpub Connector
Deposited On:24 Mar 2022 11:25
Metadata Last Modified:24 Mar 2022 11:31

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