title: Cooperative unfolding of compact conformations of the intrinsically disordered protein osteopontin.
abstract: Intrinsically disordered proteins (IDPs) constitute a class of biologically active proteins that lack defined tertiary and often secondary structure. The IDP Osteopontin (OPN), a cytokine involved in metastasis of several types of cancer, is shown to simultaneously sample extended, random coil-like conformations and stable, cooperatively folded conformations. By a combination of two magnetic resonance methods, electron paramagnetic resonance and nuclear magnetic resonance spectroscopy, we demonstrate that the OPN ensemble exhibits not only characteristics of an extended and flexible polypeptide, as expected for an IDP, but also simultaneously those of globular proteins, in particular sigmoidal structural denaturation profiles. Both types of states, extended and cooperatively folded, are populated simultaneously by OPN in its apo state. The heterogeneity of the structural properties of IDPs is thus shown to even involve cooperative folding and unfolding events.
authors.affiliation: Max Planck Institute for Polymer Research , Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kurzbach
authors.forename: Gerald
authors.initials: G
authors.lastname: Platzer
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Schwarz
authors.forename: Morkos A
authors.initials: MA
authors.lastname: Henen
authors.forename: Robert
authors.initials: R
authors.lastname: Konrat
authors.forename: Dariush
authors.initials: D
authors.lastname: Hinderberger
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D053495:Osteopontin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D058767:Protein Unfolding; D011784:Quail / Q000235:genetics / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D064267:Intrinsically Disordered Proteins; D053495:Osteopontin