Hsp72 recognizes a P binding motif in the measles virus N protein C-terminus

• Published in: Virology (New York, N.Y.) N.Y.), 2005-06, Vol.337 (1), p.162-174
• Main Authors: Zhang, Xinsheng, Bourhis, Jean-Marie, Longhi, Sonia, Carsillo, Thomas, Buccellato, Matthew, Morin, Benjamin, Canard, Bruno, Oglesbee, Michael
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Binding Sites; Cell Line; Heat-Shock Proteins - metabolism; Hsp72; HSP72 Heat-Shock Proteins; Humans - metabolism; Measles virus; Measles virus - chemistry; N protein C-terminus; Nucleocapsid Proteins - chemistry; Nucleocapsid Proteins - metabolism; Protein Binding; Virus Replication
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2005.03.035

The major inducible 70-kDa heat shock protein (hsp72) binds measles virus (MV) nucleocapsids and increases MV gene expression. The cytoplasmic tail of the MV N protein (N TAIL) contains three hydrophobic domains (Box-1–3) that are potential targets of hsp72 interaction. Low affinity binding to Box-3 is correlated to hsp72-dependent stimulation of MV minireplicon reporter gene expression whereas interactions between hsp72 and Box-1 and/or -2 have not been documented. The present work showed that virus deficient in Box-3/hsp72 interaction retains the ability to form nucleocapsid/hsp72 complexes, identifying Box-2 but not Box-1 as a mediator of high affinity hsp72 binding. Box-2 is the binding site for the viral P protein X domain (XD), where P tethers the viral polymerase to nucleocapsid in support of transcription and genome replication, and competitive inhibition of XD binding to N TAIL by hsp72 was shown. Recognition of a common binding site by P and hsp72 represents a potential mechanism for host cell modulation of viral gene expression.