title: Solution model of the intrinsically disordered polyglutamine tract-binding protein-1.
abstract: Polyglutamine tract-binding protein-1 (PQBP-1) is a 265-residue nuclear protein that is involved in transcriptional regulation. In addition to its role in the molecular pathology of the polyglutamine expansion diseases, mutations of the protein are associated with X-linked mental retardation. PQBP-1 binds specifically to glutamine repeat sequences and proline-rich regions, and interacts with RNA polymerase II and the spliceosomal protein U5-15kD. In this work, we obtained a biophysical characterization of this protein by employing complementary structural methods. PQBP-1 is shown to be a moderately compact but largely disordered molecule with an elongated shape, having a Stokes radius of 3.7 nm and a maximum molecular dimension of 13 nm. The protein is monomeric in solution, has residual β-structure, and is in a premolten globule state that is unaffected by natural osmolytes. Using small-angle x-ray scattering data, we were able to generate a low-resolution, three-dimensional model of PQBP-1.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Rees
authors.forename: Christian
authors.initials: C
authors.lastname: Gorba
authors.forename: Cesira
authors.initials: C
authors.lastname: de Chiara
authors.forename: Tam T T
authors.initials: TT
authors.lastname: Bui
authors.forename: Mitla
authors.initials: M
authors.lastname: Garcia-Maya
authors.forename: Alex F
authors.initials: AF
authors.lastname: Drake
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazawa
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
authors.forename: Dmitri
authors.initials: D
authors.lastname: Svergun
authors.forename: Yu Wai
authors.initials: YW
authors.lastname: Chen
mesh_terms: D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry*; D011487:Protein Conformation; D053838:Scattering, Small Angle; D012996:Solutions; D014961:X-Ray Diffraction
chemical_list: D009687:Nuclear Proteins; D012996:Solutions