Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design
Autor: | Andy Ka-Leung Ng, Sui-Mui Li, Paul K.S. Chan, Jia-huai Wang, Pang-Chui Shaw, Wood Yee Chan, Kemin Tan, Jin-huan Liu, Hongmin Zhang, Andrzej Joachimiak, Shannon Wing-Ngor Au, Zongli Li, Thomas Walz |
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Rok vydání: | 2008 |
Předmět: |
Protein Conformation
Viral protein Molecular Sequence Data RNA-binding protein Biology Crystallography X-Ray medicine.disease_cause Antiviral Agents Biochemistry Epitope Virus Research Communications Protein structure Genetics Influenza A virus medicine Amino Acid Sequence Molecular Biology Influenza A Virus H5N1 Subtype Viral Core Proteins RNA Virology Nucleoprotein Nucleoproteins Influenza Vaccines Drug Design Biophysics Biotechnology |
Zdroj: | The FASEB Journal. 22:3638-3647 |
ISSN: | 1530-6860 0892-6638 |
DOI: | 10.1096/fj.08-112110 |
Popis: | The threat of a pandemic outbreak of influenza virus A H5N1 has become a major concern worldwide. The nucleoprotein (NP) of the virus binds the RNA genome and acts as a key adaptor between the virus and the host cell. It, therefore, plays an important structural and functional role and represents an attractive drug target. Here, we report the 3.3-Å crystal structure of H5N1 NP, which is composed of a head domain, a body domain, and a tail loop. Our structure resolves the important linker segments (residues 397–401, 429–437) that connect the tail loop with the remainder of the molecule and a flexible, basic loop (residues 73–91) located in an arginine-rich groove surrounding Arg150. Using surface plasmon resonance, we found the basic loop and arginine-rich groove, but mostly a protruding element containing Arg174 and Arg175, to be important in RNA binding by NP. We also used our crystal structure to build a ring-shaped assembly of nine NP subunits to model the miniribonucleoprotein particle previously visualized by electron microscopy. Our study of H5N1 NP provides insight into the oligomerization interface and the RNA-binding groove, which are attractive drug targets, and it identifies the epitopes that might be used for universal vaccine development.—Ng, A. K.-L., Zhang, H., Tan, K., Li, Z., Liu, J.-h., Chan, P. K.-S., Li, S.-M., Chan, W.-Y., Au, S. W.-N., Joachimiak, A., Walz, T., Wang, J.-H., Shaw, P.-C. Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design. |
Databáze: | OpenAIRE |
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