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

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The nucleoprotein of measles virus consists of an N-terminal domain, N CORE (aa 1–400), resistant to proteolysis, and a C-terminal domain, N TAIL (aa 401–525), hypersensitive to proteolysis and not visible by electron microscopy. Using two complementary computational approaches, we predict that N TAIL belongs to the class of natively unfolded proteins. Using different biochemical and biophysical approaches, we show that N TAIL is indeed unstructured in solution. In particular, the spectroscopic and hydrodynamic properties of N TAIL indicate that this protein domain belongs to the premolten globule subfamily within the class of intrinsically disordered proteins. The isolated N TAIL 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 N TAIL 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 N TAIL (N TAIL2, aa 401–488) devoid of the α-MoRE. We show that N TAIL2 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 N TAIL2 and N TAIL using circular dichroism in the presence of 2,2,2-trifluoroethanol. We show that N TAIL2 has a lower α-helical potential compared to N TAIL, thus suggesting that the α-MoRE may be indeed involved in the induced folding of N TAIL.