title: Folding propensity of intrinsically disordered proteins by osmotic stress.
abstract: Proteins imparted with intrinsic disorder conduct a range of essential cellular functions. To better understand the folding and hydration properties of intrinsically disordered proteins (IDPs), we used osmotic stress to induce conformational changes in nuclear co-activator binding domain (NCBD) and activator for thyroid hormone and retinoid receptor (ACTR) separate from their mutual binding. Osmotic stress was applied by the addition of small and polymeric osmolytes, where we discovered that water contributions to NCBD folding always exceeded those for ACTR. Both NCBD and ACTR were found to gain α-helical structure with increasing osmotic stress, consistent with their folding upon NCBD/ACTR complex formation. Using small-angle neutron scattering (SANS), we further characterized NCBD structural changes with the osmolyte ethylene glycol. Here a large reduction in overall size initially occurred before substantial secondary structural change. By focusing on folding propensity, and linked hydration changes, we uncover new insights that may be important for how IDP folding contributes to binding.
authors.affiliation: Department of Medicine, Graduate School of Medicine, University of Tennessee, Health Science Center, Knoxville, TN, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Mansouri
authors.affiliation: Department of Medicine, Graduate School of Medicine, University of Tennessee, Health Science Center, Knoxville, TN, USA and Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA. stanleycb@ornl.gov.
authors.forename: Laura N
authors.initials: LN
authors.lastname: Grese
authors.affiliation: Department of Medicine, Graduate School of Medicine, University of Tennessee, Health Science Center, Knoxville, TN, USA and Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA. stanleycb@ornl.gov.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Rowe
authors.affiliation: Health Data Sciences Institute, Computational Science and Engineering Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Pino
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: S Chakra
authors.initials: SC
authors.lastname: Chennubhotla
authors.affiliation: Health Data Sciences Institute, Computational Science and Engineering Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Ramanathan
authors.affiliation: Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA. stanleycb@ornl.gov.
authors.forename: Hugh M
authors.initials: HM
authors.lastname: O'Neill
authors.affiliation: Department of Medicine, Graduate School of Medicine, University of Tennessee, Health Science Center, Knoxville, TN, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Berthelier
authors.affiliation: Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA. stanleycb@ornl.gov.
authors.forename: Christopher B
authors.identifier: 0000-0002-4226-7710
authors.initials: CB
authors.lastname: Stanley
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D009997:Osmotic Pressure; D011485:Protein Binding; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary
chemical_list: D064267:Intrinsically Disordered Proteins