title: Compaction properties of an intrinsically disordered protein: Sic1 and its kinase-inhibitor domain.
abstract: IDPs in their unbound state can transiently acquire secondary and tertiary structure. Describing such intrinsic structure is important to understand the transition between free and bound state, leading to supramolecular complexes with physiological interactors. IDP structure is highly dynamic and, therefore, difficult to study by conventional techniques. This work focuses on conformational analysis of the KID fragment of the Sic1 protein, an IDP with a key regulatory role in the cell-cycle of Saccharomyces cerevisiae. FT-IR spectroscopy, ESI-MS, and IM measurements are used to capture dynamic and short-lived conformational states, probing both secondary and tertiary protein structure. The results indicate that the isolated Sic1 KID retains dynamic helical structure and populates collapsed states of different compactness. A metastable, highly compact species is detected. Comparison between the fragment and the full-length protein suggests that chain length is crucial to the stabilization of compact states of this IDP. The two proteins are compared by a length-independent compaction index.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Brocca
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Testa
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.forename: Maria
authors.initials: M
authors.lastname: Samalikova
authors.forename: Antonino
authors.initials: A
authors.lastname: Natalello
authors.forename: Elena
authors.initials: E
authors.lastname: Papaleo
authors.forename: Marina
authors.initials: M
authors.lastname: Lotti
authors.forename: Luca
authors.initials: L
authors.lastname: De Gioia
authors.forename: Silvia Maria
authors.initials: SM
authors.lastname: Doglia
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.forename: Rita
authors.initials: R
authors.lastname: Grandori
mesh_terms: D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000737:chemistry* / Q000378:metabolism*; D057446:Hydrodynamics; D008969:Molecular Sequence Data; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D047428:Protein Kinase Inhibitors; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins