Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design
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AbstractThe 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-angstrom 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 397401, 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.
All Author(s) ListNg AKL, Zhang HM, Tan KM, Li ZL, Liu JH, Chan PKS, Li SM, Chan WY, Au SWN, Joachimiak A, Walz T, Wang JH, Shaw PC
Journal nameFASEB Journal
Volume Number22
Issue Number10
PublisherFederation of American Society of Experimental Biology (FASEB)
Pages3638 - 3647
LanguagesEnglish-United Kingdom
Keywordscrystal structure; protein-RNA interaction; trimerization
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Biology; BIOLOGY; Cell Biology; CELL BIOLOGY; Life Sciences & Biomedicine - Other Topics

Last updated on 2021-15-09 at 04:22