Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells.
Identifieur interne : 002095 ( PubMed/Corpus ); précédent : 002094; suivant : 002096Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells.
Auteurs : Yong Wah Tan ; Shouguo Fang ; Hui Fan ; Julien Lescar ; D X LiuSource :
- Nucleic acids research [ 1362-4962 ] ; 2006.
English descriptors
- KwdEn :
- Amino Acid Sequence, Amino Acid Substitution, Amino Acids, Animals, Chlorocebus aethiops, DNA Mutational Analysis, Infectious bronchitis virus (genetics), Infectious bronchitis virus (growth & development), Molecular Sequence Data, Nucleocapsid Proteins (chemistry), Nucleocapsid Proteins (genetics), Nucleocapsid Proteins (metabolism), Protein Structure, Tertiary, RNA, Viral (biosynthesis), RNA, Viral (metabolism), RNA-Binding Proteins (chemistry), RNA-Binding Proteins (genetics), RNA-Binding Proteins (metabolism), Sequence Alignment, Vero Cells.
- MESH :
- chemical , biosynthesis : RNA, Viral.
- chemical , chemistry : Nucleocapsid Proteins, RNA-Binding Proteins.
- chemical , genetics : Nucleocapsid Proteins, RNA-Binding Proteins.
- chemical , metabolism : Nucleocapsid Proteins, RNA, Viral, RNA-Binding Proteins.
- chemical : Amino Acids.
- genetics : Infectious bronchitis virus.
- growth & development : Infectious bronchitis virus.
- Amino Acid Sequence, Amino Acid Substitution, Animals, Chlorocebus aethiops, DNA Mutational Analysis, Molecular Sequence Data, Protein Structure, Tertiary, Sequence Alignment, Vero Cells.
Abstract
The N-terminal domain of the coronavirus nucleocapsid (N) protein adopts a fold resembling a right hand with a flexible, positively charged beta-hairpin and a hydrophobic palm. This domain was shown to interact with the genomic RNA for coronavirus infectious bronchitis virus (IBV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Based on its 3D structure, we used site-directed mutagenesis to identify residues essential for the RNA-binding activity of the IBV N protein and viral infectivity. Alanine substitution of either Arg-76 or Tyr-94 in the N-terminal domain of IBV N protein led to a significant decrease in its RNA-binding activity and a total loss of the infectivity of the viral RNA to Vero cells. In contrast, mutation of amino acid Gln-74 to an alanine, which does not affect the binding activity of the N-terminal domain, showed minimal, if any, detrimental effect on the infectivity of IBV. This study thus identifies residues critical for RNA binding on the nucleocapsid surface, and presents biochemical and genetic evidence that directly links the RNA binding capacity of the coronavirus N protein to the viral infectivity in cultured cells. This information would be useful in development of preventive and treatment approaches against coronavirus infection.
DOI: 10.1093/nar/gkl650
PubMed: 16971454
Links to Exploration step
pubmed:16971454Le document en format XML
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This domain was shown to interact with the genomic RNA for coronavirus infectious bronchitis virus (IBV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Based on its 3D structure, we used site-directed mutagenesis to identify residues essential for the RNA-binding activity of the IBV N protein and viral infectivity. Alanine substitution of either Arg-76 or Tyr-94 in the N-terminal domain of IBV N protein led to a significant decrease in its RNA-binding activity and a total loss of the infectivity of the viral RNA to Vero cells. In contrast, mutation of amino acid Gln-74 to an alanine, which does not affect the binding activity of the N-terminal domain, showed minimal, if any, detrimental effect on the infectivity of IBV. This study thus identifies residues critical for RNA binding on the nucleocapsid surface, and presents biochemical and genetic evidence that directly links the RNA binding capacity of the coronavirus N protein to the viral infectivity in cultured cells. This information would be useful in development of preventive and treatment approaches against coronavirus infection.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16971454</PMID><DateCompleted><Year>2006</Year><Month>11</Month><Day>06</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1362-4962</ISSN><JournalIssue CitedMedium="Internet"><Volume>34</Volume><Issue>17</Issue><PubDate><Year>2006</Year></PubDate></JournalIssue><Title>Nucleic acids research</Title><ISOAbbreviation>Nucleic Acids Res.</ISOAbbreviation></Journal><ArticleTitle>Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells.</ArticleTitle><Pagination><MedlinePgn>4816-25</MedlinePgn></Pagination><Abstract><AbstractText>The N-terminal domain of the coronavirus nucleocapsid (N) protein adopts a fold resembling a right hand with a flexible, positively charged beta-hairpin and a hydrophobic palm. This domain was shown to interact with the genomic RNA for coronavirus infectious bronchitis virus (IBV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Based on its 3D structure, we used site-directed mutagenesis to identify residues essential for the RNA-binding activity of the IBV N protein and viral infectivity. Alanine substitution of either Arg-76 or Tyr-94 in the N-terminal domain of IBV N protein led to a significant decrease in its RNA-binding activity and a total loss of the infectivity of the viral RNA to Vero cells. In contrast, mutation of amino acid Gln-74 to an alanine, which does not affect the binding activity of the N-terminal domain, showed minimal, if any, detrimental effect on the infectivity of IBV. This study thus identifies residues critical for RNA binding on the nucleocapsid surface, and presents biochemical and genetic evidence that directly links the RNA binding capacity of the coronavirus N protein to the viral infectivity in cultured cells. This information would be useful in development of preventive and treatment approaches against coronavirus infection.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Yong Wah</ForeName><Initials>YW</Initials><AffiliationInfo><Affiliation>Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fang</LastName><ForeName>Shouguo</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Hui</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Lescar</LastName><ForeName>Julien</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>D X</ForeName><Initials>DX</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, 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development</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019590" MajorTopicYN="N">Nucleocapsid Proteins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017434" MajorTopicYN="N">Protein Structure, Tertiary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012367" MajorTopicYN="N">RNA, Viral</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016601" MajorTopicYN="N">RNA-Binding Proteins</DescriptorName><QualifierName UI="Q000737" 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