The C-terminal domain of measles virus nucleoprotein belongs to the class of intrinsically disordered proteins that fold upon binding to their physiological partner

The nucleoprotein of measles virus consists of an N-terminal domain, NCORE (aa 1–400), resistant to proteolysis, and a C-terminal domain, NTAIL (aa 401–525), hypersensitive to proteolysis and not visible by electron microscopy. Using two complementary computational approaches, we predict that NTAIL belongs to the class of natively unfolded proteins. Using different biochemical and biophysical approaches, we show that NTAIL is indeed unstructured in solution. In particular, the spectroscopic and hydrodynamic properties of NTAIL indicate that this protein domain belongs to the premolten globule subfamily within the class of intrinsically disordered proteins. The isolated NTAIL domain was shown to be able to bind to its physiological partner, the phosphoprotein (P), and to undergo an induced folding upon binding to the C-terminal moiety of P [J. Biol. Chem. 278 (2003) 18638]. Using a computational analysis, we have identified within NTAIL a putative α-helical molecular recognition element (α-MoRE, aa 488–499), which could be involved in binding to P via induced folding. We report the bacterial expression and purification of a truncated form of NTAIL (NTAIL2, aa 401–488) devoid of the α-MoRE. We show that NTAIL2 has lost the ability to bind to P, thus supporting the hypothesis that the α-MoRE may play a role in binding to P. We have further analyzed the α-helical propensities of NTAIL2 and NTAIL using circular dichroism in the presence of 2,2,2-trifluoroethanol. We show that NTAIL2 has a lower α-helical potential compared to NTAIL, thus suggesting that the α-MoRE may be indeed involved in the induced folding of NTAIL.