Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses.

Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. Research Abstract Details 

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Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. Abstract Text:

Cuifeng Yin,Javed A Khan,G V T Swapna,Asli Ertekin,Robert M Krug,Liang Tong,Gaetano T Montelione,

Influenza A viruses cause a highly contagious respiratory disease in humans and are responsible for periodic widespread epidemics with high mortality rates. The influenza A virus NS1 protein (NS1A) plays a key role in countering host antiviral defense and in virulence. The 73-residue N-terminal domain of NS1A (NS1A-(1-73)) forms a symmetric homodimer with a unique six-helical chain fold. It binds canonical A-form double-stranded RNA (dsRNA). Mutational inactivation of this dsRNA binding activity of NS1A highly attenuates virus replication. Here, we have characterized the unique structural features of the dsRNA binding surface of NS1A-(1-73) using NMR methods and describe the 2.1-A x-ray crystal structure of the corresponding dsRNA binding domain from human influenza B virus NS1B-(15-93). These results identify conserved dsRNA binding surfaces on both NS1A-(1-73) and NS1B-(15-93) that are very different from those indicated in earlier "working models" of the complex between dsRNA and NS1A-(1-73). The combined NMR and crystallographic data reveal highly conserved surface tracks of basic and hydrophilic residues that interact with dsRNA. These tracks are structurally complementary to the polyphosphate backbone conformation of A-form dsRNA and run at an approximately 45 degrees angle relative to the axes of helices alpha2/alpha2'. At the center of this dsRNA binding epitope, and common to NS1 proteins from influenza A and B viruses, is a deep pocket that includes both hydrophilic and hydrophobic amino acids. This pocket provides a target on the surface of the NS1 protein that is potentially suitable for the development of antiviral drugs targeting both influenza A and B viruses.

Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. Publishing Authors By Initials

C Yin,JA Khan,GV Swapna,A Ertekin,RM Krug,L Tong,GT Montelione,

For similar proteins: viral proteins: viral nonstructural proteins research abstracts see: proteins: viral proteins: viral nonstructural proteins research

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Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 20584-92

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 1

MONTH: 05

YEAR: 2007

Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. Keywords Mesh Terms:

KEYWORDS: Viral Nonstructural Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. Information

Substance Name: Viral Nonstructural Proteins

Registry Number: 0

Grant and Affiliation Information for Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses.

AFFILIATION: Center for Advanced Biotechnology and Medicine, Northeast Structural Genomics Consortium, Department of Molecular Biology and Biochemistry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: U54 GM 074958

ACRONYM: GM

MEDLINETA: J Biol Chem

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