{
   "source_x": "PMC",
   "title": "Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9",
   "doi": "http://dx.doi.org/10.1002/pro.3150",
   "pmcid": "PMC5405427",
   "abstract": "The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15\u201316 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single\u2010stranded RNA. Thus, disrupting nsp9 dimerization is a potential anti\u2010CoV therapy. However, different nsp9 dimer forms have been reported for alpha\u2010 and beta\u2010CoVs, and no structural information is available for gamma\u2010CoVs. Here we determined the crystal structure of nsp9 from the avian infectious bronchitis virus (IBV), a representative gamma\u2010CoV that affects the economy of the poultry industry because it can infect domestic fowl. IBV nsp9 forms a homodimer via interactions across a hydrophobic interface, which consists of two parallel alpha helices near the carboxy terminus of the protein. The IBV nsp9 dimer resembles that of SARS\u2010CoV nsp9, indicating that this type of dimerization is conserved among all CoVs. This makes disruption of the dimeric interface an excellent strategy for developing anti\u2010CoV therapies. To facilitate this effort, we characterized the roles of six conserved residues on this interface using site\u2010directed mutagenesis and a multitude of biochemical and biophysical methods. We found that three residues are critical for nsp9 dimerization and its abitlity to bind RNA.",
   "authors": [
      "['Hu, Tingting', 'Chen, Cheng', 'Li, Huiyan', 'Dou, Yanshu', 'Zhou, Ming', 'Lu, Deren', 'Zong, Qi', 'Li, Yulei', 'Yang, Cheng', 'Zhong, Zhihui', 'Singh, Namit', 'Hu, Honggang', 'Zhang, Rundong', 'Yang, Haitao', 'Su, Dan']"
   ],
   "id": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405427"
}