Bluetongue virus (BTV) non-structural protein 2 (NS2) belongs to a class of highly conserved proteins found in members of the orbivirus genus of the reoviridae. NS2 forms large multimeric complexes, localizes to cytoplasmic inclusion bodies in the infected cells and binds non-sequence specifically single-stranded RNA (ssRNA). Due to its ability to bind ssRNA, it has been suggested that the protein is involved in the selection and condensation of the BTV ssRNA segments prior to genome encapsidation. We have previously determined the crystal structure of the 177 amino acid N-terminal domain, sufficient for ssRNA binding ability of NS2, to 2.4 angstrom resolution. The G terminal domain, as determined at low resolution using small-angle X-ray scattering, is an elongated dimer. This domain expressed in insect cells is phosphorylated at S249 and S259. Electron microscopy of the full-length protein shows a variety of species with the largest having a ring-like appearance. Based on the electron micrographs, the crystal structure of the N-terminal domain and the structure of the C-terminal domain reported here, we propose a model for a decamer of the full-length protein. This decamer changes conformation upon binding of a non-hydrolysable ATP analogue. (C) 2007 Elsevier Inc. All rights reserved.