Crystal structure of the measles virus phosphoprotein domain responsible for the induced folding of the C-terminal domain of the nucleoprotein

J Biol Chem. 2003 Nov 7;278(45):44567-73. doi: 10.1074/jbc.M308745200. Epub 2003 Aug 27.

Abstract

Measles virus is a negative-sense, single-stranded RNA virus belonging to the Mononegavirales order which comprises several human pathogens such as Ebola, Nipah, and Hendra viruses. The phosphoprotein of measles virus is a modular protein consisting of an intrinsically disordered N-terminal domain (Karlin, D., Longhi, S., Receveur, V., and Canard, B. (2002) Virology 296, 251-262) and of a C-terminal moiety (PCT) composed of alternating disordered and globular regions. We report the crystal structure of the extreme C-terminal domain (XD) of measles virus phosphoprotein (aa 459-507) at 1.8 A resolution. We have previously reported that the C-terminal domain of measles virus nucleoprotein, NTAIL, is intrinsically unstructured and undergoes induced folding in the presence of PCT (Longhi, S., Receveur-Brechot, V., Karlin, D., Johansson, K., Darbon, H., Bhella, D., Yeo, R., Finet, S., and Canard, B. (2003) J. Biol. Chem. 278, 18638-18648). Using far-UV circular dichroism, we show that within PCT, XD is the region responsible for the induced folding of NTAIL. The crystal structure of XD consists of three helices, arranged in an anti-parallel triple-helix bundle. The surface of XD formed between helices alpha2 and alpha3 displays a long hydrophobic cleft that might provide a complementary hydrophobic surface to embed and promote folding of the predicted alpha-helix of NTAIL. We present a tentative model of the interaction between XD and NTAIL. These results, beyond presenting the first measles virus protein structure, shed light both on the function of the phosphoprotein at the molecular level and on the process of induced folding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Circular Dichroism
  • Cloning, Molecular
  • Crystallization
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Gene Expression
  • Light
  • Measles virus / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Nucleocapsid Proteins
  • Nucleoproteins / chemistry*
  • Nucleoproteins / genetics
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Phosphoproteins / chemistry*
  • Phosphoproteins / genetics
  • Protein Folding
  • Recombinant Proteins
  • Scattering, Radiation
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics

Substances

  • Nucleocapsid Proteins
  • Nucleoproteins
  • Peptide Fragments
  • Phosphoproteins
  • Recombinant Proteins
  • Viral Proteins
  • nucleoprotein, Measles virus

Associated data

  • PDB/1OKS
  • PDB/1OKSSF