1XEQ

Crystal tructure of RNA binding domain of influenza B virus non-structural protein

Summary for 1XEQ

• Entry DOI: 10.2210/pdb1xeq/pdb
• Related: 1NS1
• Descriptor: Nonstructural protein NS1, BROMIDE ION (3 entities in total)
• Functional Keywords: influenza b virus, rna binding domain, non-structural protein, ns1b, structural genomics, psi, protein structure initiative, northeast structural genomics consortium, nesg, viral protein
• Biological source: Influenza B virus (B/Lee/40)
• Total number of polymer chains: 2
• Total formula weight: 25281.45

Authors

Khan, J.A.,Yin, C.,Krug, R.M.,Montelione, G.T.,Tong, L.,Northeast Structural Genomics Consortium (NESG) (deposition date: 2004-09-11, release date: 2005-09-20, Last modification date: 2024-02-14)

Primary citation

Yin, C.,Khan, J.A.,Swapna, G.V.,Ertekin, A.,Krug, R.M.,Tong, L.,Montelione, G.T.
Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses.
J.Biol.Chem., 282:20584-20592, 2007

PubMed Abstract: 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.

PubMed: 17475623
DOI: 10.1074/jbc.M611619200

Experimental method

X-RAY DIFFRACTION (2.1 Å)