Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design
Top Cited Papers
- 30 June 2008
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 22 (10), 3638-3647
- https://doi.org/10.1096/fj.08-112110
Abstract
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-A 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.Keywords
Funding Information
- National Institutes of Health
This publication has 32 references indexed in Scilit:
- Cross-Recognition of Avian H5N1 Influenza Virus by Human Cytotoxic T-Lymphocyte Populations Directed to Human Influenza A VirusJournal of Virology, 2008
- Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virusThe Journal of Experimental Medicine, 2008
- The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNANature, 2006
- Fitness costs limit escape from cytotoxic T lymphocytes by influenza A virusesVaccine, 2006
- ArchPRED: a template based loop structure prediction serverNucleic Acids Research, 2006
- The Hypervariable Immunodominant NP418-426Epitope from the Influenza A Virus Nucleoprotein Is Recognized by Cytotoxic T Lymphocytes with High Functional AvidityJournal of Virology, 2006
- Functional Constraints of Influenza A Virus Epitopes Limit Escape from Cytotoxic T LymphocytesJournal of Virology, 2005
- Coot: model-building tools for molecular graphicsActa crystallographica. Section D, Structural biology, 2004
- Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytesVirus Research, 2004
- The CCP4 suite: programs for protein crystallographyActa crystallographica. Section D, Structural biology, 1994