Abstract
The hantaviruses are emerging infectious viruses that in humans can cause a cardiopulmonary syndrome or a hemorrhagic fever with renal syndrome. The nucleocapsid (N) is the most abundant viral protein, and during viral assembly, the N protein forms trimers and packages the viral RNA genome. Here, we report the NMR structure of the N-terminal domain (residues 1-74, called N1-74) of the Andes hantavirus N protein. N1-74 forms two long helices (alpha1 and alpha2) that intertwine into a coiled coil domain. The conserved hydrophobic residues at the helix alpha1-alpha2 interface stabilize the coiled coil; however, there are many conserved surface residues whose function is not known. Site-directed mutagenesis, CD spectroscopy, and immunocytochemistry reveal that a point mutation in the conserved basic surface formed by Arg22 or Lys26 lead to antibody recognition based on the subcellular localization of the N protein. Thus, Arg22 and Lys26 are likely involved in a conformational change or molecular recognition when the N protein is trafficked from the cytoplasm to the Golgi, the site of viral assembly and maturation.