1. Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street, MS140, Houston, Texas 77005, USA
2. Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway, Austin, Texas 78712-1095, USA

Correspondence to: Yizhi Jane Tao¹ Correspondence and requests for materials should be addressed to Y.J.T (Email: ytao@rice.edu).

Abstract

Influenza A viruses pose a serious threat to world public health, particularly the currently circulating avian H5N1 viruses. The influenza viral nucleoprotein forms the protein scaffold of the helical genomic ribonucleoprotein complexes, and has a critical role in viral RNA replication¹. Here we report a 3.2 Å crystal structure of this nucleoprotein, the overall shape of which resembles a crescent with a head and a body domain, with a protein fold different compared with that of the rhabdovirus nucleoprotein^{2, 3}. Oligomerization of the influenza virus nucleoprotein is mediated by a flexible tail loop that is inserted inside a neighbouring molecule. This flexibility in the tail loop enables the nucleoprotein to form loose polymers as well as rigid helices, both of which are important for nucleoprotein functions. Single residue mutations in the tail loop result in the complete loss of nucleoprotein oligomerization. An RNA-binding groove, which is found between the head and body domains at the exterior of the nucleoprotein oligomer, is lined with highly conserved basic residues widely distributed in the primary sequence. The nucleoprotein structure shows that only one of two proposed nuclear localization signals are accessible, and suggests that the body domain of nucleoprotein contains the binding site for the viral polymerase. Our results identify the tail loop binding pocket as a potential target for antiviral development.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.