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, 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 TA...

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Bibliographic Details
Published in:Virus research 2004-02, Vol.99 (2), p.157-167
Main Authors: Bourhis, Jean-Marie, Johansson, Kenth, Receveur-Bréchot, Véronique, Oldfield, Christopher J., Dunker, Keith A., Canard, Bruno, Longhi, Sonia
Format: Article
Language:English
Subjects:
Circular Dichroism
Computational Biology
Induced folding
Intrinsic disorder
Measles virus
Measles virus - chemistry
Molecular recognition element
Nucleoprotein
Nucleoproteins - chemistry
Nucleoproteins - genetics
Nucleoproteins - isolation & purification
Nucleoproteins - metabolism
Paramyxoviridae
Phosphoprotein
Phosphoproteins - metabolism
Protein Binding
Protein Conformation
Protein Folding
Protein Structure, Secondary
Recombinant Proteins - biosynthesis
Recombinant Proteins - chemistry
Recombinant Proteins - isolation & purification
Recombinant Proteins - metabolism
Sequence Deletion
Viral Proteins - chemistry
Viral Proteins - genetics
Viral Proteins - isolation & purification
Viral Proteins - metabolism
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Summary: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.
ISSN:0168-1702
1872-7492
DOI:10.1016/j.virusres.2003.11.007