title: Molecular basis for structural heterogeneity of an intrinsically disordered protein bound to a partner by combined ESI-IM-MS and modeling.
abstract: Intrinsically disordered proteins (IDPs) form biologically active complexes that can retain a high degree of conformational disorder, escaping structural characterization by conventional approaches. An example is offered by the complex between the intrinsically disordered N(TAIL) domain and the phosphoprotein X domain (P(XD)) from measles virus (MeV). Here, distinct conformers of the complex are detected by electrospray ionization-mass spectrometry (ESI-MS) and ion mobility (IM) techniques yielding estimates for the solvent-accessible surface area (SASA) in solution and the average collision cross-section (CCS) in the gas phase. Computational modeling of the complex in solution, based on experimental constraints, provides atomic-resolution structural models featuring different levels of compactness. The resulting models indicate high structural heterogeneity. The intermolecular interactions are predominantly hydrophobic, not only in the ordered core of the complex, but also in the dynamic, disordered regions. Electrostatic interactions become involved in the more compact states. This system represents an illustrative example of a hydrophobic complex that could be directly detected in the gas phase by native mass spectrometry. This work represents the first attempt to modeling the entire N(TAIL) domain bound to P(XD) at atomic resolution.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126, Milan, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: D'Urzo
authors.forename: Albert
authors.initials: A
authors.lastname: Konijnenberg
authors.forename: Giulia
authors.initials: G
authors.lastname: Rossetti
authors.forename: Johnny
authors.initials: J
authors.lastname: Habchi
authors.forename: Jinyu
authors.initials: J
authors.lastname: Li
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.forename: Sonia
authors.initials: S
authors.lastname: Longhi
authors.forename: Rita
authors.initials: R
authors.lastname: Grandori
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008459:Measles virus; D008958:Models, Molecular; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014764:Viral Proteins / Q000737:chemistry
chemical_list: D064267:Intrinsically Disordered Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins