Experimental Characterization of Fuzzy Protein Assemblies: Interactions of Paramyxoviral NTAIL Domains With Their Functional Partners

Methods Enzymol. 2018:611:137-192. doi: 10.1016/bs.mie.2018.08.006. Epub 2018 Oct 5.

Abstract

In this chapter we detail various experimental approaches to characterize the fuzziness of complexes made of the C-terminal domain of the nucleoprotein (NTAIL) from three representative paramyxoviruses and of the C-terminal X domain (XD) of the homologous phosphoprotein. We discuss the advantages, the limitations, as well as the caveats of the various methods. We describe experimental data showing that paramyxoviral NTAIL-XD complexes are characterized by a considerable amount of conformational heterogeneity. We also detail recent data that revealed that NTAIL is highly malleable, i.e., it displays a partner-mediated polymorphism. All the results suggest that NTAIL plasticity and fuzziness play a role in the coordination and regulation of the NTAIL interaction network so as to ensure efficient transcription and replication.

Keywords: ESI-MS and IM-MS; Experimental assessment of fuzziness; Fuzzy interactions; Impact of fuzziness on binding; Kinetics; Mutagenesis; NMR; Protein complementation assays; SAXS; SEC; Site-directed spin-labeling EPR spectroscopy; Split-GFP reassembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Gel / methods
  • Electron Spin Resonance Spectroscopy / methods
  • Models, Molecular
  • Mutagenesis
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Nucleoproteins / chemistry
  • Nucleoproteins / genetics
  • Nucleoproteins / metabolism*
  • Paramyxoviridae / chemistry
  • Paramyxoviridae / genetics
  • Paramyxoviridae / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Protein Interaction Mapping / methods*
  • Scattering, Small Angle
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • X-Ray Diffraction

Substances

  • Nucleoproteins
  • Phosphoproteins
  • Viral Proteins