Solution Model of the Intrinsically Disordered Polyglutamine Tract-Binding Protein-1

DOI: 10.1016/j.bpj.2012.02.047

Authors: Martin Rees (King's College London) , Christian Gorba (European Molecular Biology Laboratory) , Cesira De chiara (Medical Research Council National Institute of Medical Research) , Tam t.t. Bui (King's College London) , Mitla Garcia-maya (King's College London) , Alex f. Drake (King's College London) , Hitoshi Okazawa (Tokyo Medical and Dental University) , Annalisa Pastore (Medical Research Council National Institute of Medical Research) , Dmitri Svergun (European Molecular Biology Laboratory) , Yu Wai Chen (King's College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biophysical Journal , VOL 102 (7) , PAGES 1608 - 1616

State: Published (Approved)
Published: April 2012

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 ?-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.

Subject Areas: Biology and Bio-materials, Physics, Medicine


Instruments: B23-Circular Dichroism

Other Facilities: DESY