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- Title
Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design.
- Authors
Ka-Leung Ng, Andy; Hongmin Zhang; Kemin Tan; Zongli Li; Jin-huan Liu; Kay-Sheung Chan, Paul; Sui-Mui Li; Wood-Yee Chan; Shannon Wing-Ngor Au; Joachimiak, Andrzej; Walz, Thomas; Jia-Huai Wang; Pang-Chui Shaw
- 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-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 miniribonucleo-protein 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.
- Subjects
INFLUENZA A virus; NUCLEOPROTEINS; RNA; PROTEIN binding; OLIGOMERS; INFLUENZA vaccines; DRUG design; TARGETED drug delivery
- Publication
FASEB Journal, 2008, Vol 22, Issue 10, p3638
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.08-112110