Solution model of the intrinsically disordered polyglutamine tract-binding protein-1

TY - JOUR

T1 - Solution model of the intrinsically disordered polyglutamine tract-binding protein-1

AU - Rees, Martin

AU - Gorba, Christian

AU - de Chiara, Cesira

AU - Bui, Tam T. T.

AU - Garcia-Maya, Mitla

AU - Drake, Alex F.

AU - Okazawa, Hitoshi

AU - Pastore, Annalisa

AU - Svergun, Dmitri

AU - Chen, Yu Wai

N1 - Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

PY - 2012/4/4

Y1 - 2012/4/4

N2 - 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 beta-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.

AB - 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 beta-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.

KW - Nuclear Proteins

KW - X-Ray Diffraction

KW - Models, Molecular

KW - Scattering, Small Angle

KW - Solutions

KW - Protein Conformation

U2 - 10.1016/j.bpj.2012.02.047

DO - 10.1016/j.bpj.2012.02.047

M3 - Article

C2 - 22500761

SN - 1542-0086

VL - 102

SP - 1608

EP - 1616

JO - Biophysical Journal

JF - Biophysical Journal

IS - 7

ER -