Neutralizing antibody in mouse and monkey serum was quantitated by a plaque reduction neutralization assay. Test sera were heat inactivated (56°C for 30 minutes) and serial 2-fold dilutions beginning at 1:5 or 1:10 were prepared in OptiMEM (Invitrogen) supplemented with 2% FBS, 50 µg/ml gentamicin, and 0.5% human albumin (Talecris Biotherapeutics, Inc., Research Triangle Park, NC). The homologous LACV was diluted to a final titer of 500 PFU/ml in the same diluent and 10% guinea pig complement (Cambrex Bioscience Walkersville, Inc., Walkersville, MD) was added to equal volumes of the serum dilutions and mixed well. Serum/virus mixture was incubated at 37°C for 30 minutes, added to confluent monolayers of Vero cells, and incubated for 1 hour to allow virus attachment. Cells were overlayed with 1% methylcellulose and incubated for 5 days at 37°C. After incubation, the overlay was removed, and the monolayers were washed twice with PBS and stained with crystal violet to allow for the enumeration of virus plaques. A 60% plaque-reduction neutralization titer was calculated. The intrinsically disordered C‐terminal domain of the measles virus nucleoprotein interacts with the C‐terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded Measles virus is a negative‐sense, single‐stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. Themeasles virus nucleoprotein consists of a structured N‐terminal domain, and of an intrinsically disordered C‐terminal domain, N(TAIL) (aa 401–525), which undergoes induced folding in the presence of the C‐terminal domain (XD, aa 459–507) of the viral phosphoprotein. With in N(TAIL), an α‐helical molecular recognition element (α‐MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small‐angle X‐ray scattering, we have derived a low‐resolution structural model of the complex between XD and N(TAIL), which shows that most of N(TAIL) remains disordered in the complex despite P‐induced folding within the α‐MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N‐terminal region of N(TAIL), and of a bulky globular region, corresponding to XD and to the C terminus of N(TAIL) (aa 486–525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that N(TAIL) has an additional site (aa 517–525) involved in binding to XD but not in the unstructured‐to‐structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure. Nucleoproteins of Paramyxoviridae are divided into two regions: a structured N-terminal moiety, N CORE (aa 1-400 in MV), which contains all the regions necessary for self-assembly and RNA-binding Curran et al. 1993; Bankamp et al. 1996; Liston et al. 1997; Myers et al. 1997b Myers et al. , 1999 Karlin et al. 2002a; Kingston et al. 2004b) , and a C-terminal domain, N TAIL . N TAIL is intrinsically unstructured (i.e., it lacks any stable secondary and tertiary structure in physiological conditions) ) and is exposed at the surface of the viral nucleocapsid (Heggeness et al. 1980 (Heggeness et al. , 1981 . The presence of a flexible region protruding from the viral nucleocapsid allows the establishment of interactions with numerous different viral partners and with several cellular proteins (Moyer et al. 1990 ; De and Banerjee 1999; tenOever et al. 2002; Zhang et al. 2002; Laine et al. 2003) . In Morbilliviruses and Respiroviruses, N TAIL is responsible for binding to P (Curran et al. 1993; Harty and Palese 1995; Bankamp et al. 1996; Liston et al. 1997; Longhi et al. 2003; Kingston et al. 2004b) , to the polymerase complex P-L, and to the matrix protein (Coronel et al. 2001) . Beyond viral partners, N TAIL also interacts with several cellular proteins, including the interferon regulatory factor 3 (tenOever et al. 2002) and the heat-shock protein Hsp72 (Zhang et al. 2002) . Moreover, N TAIL within viral nucleocapsids released from infected cells also binds to a yet unidentified protein receptor expressed at the surface of human thymic epithelial cells (Laine et al. 2003 (Laine et al. , 2005 .