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This content will become publicly available on October 11, 2017

Title: Folding propensity of intrinsically disordered proteins by osmotic stress

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). 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 a-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. In conclusion, 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:
 [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [3] ;  [3] ;  [1] ;  [3]
  1. Univ. of Tennessee, Knoxville, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  3. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  4. Univ. of Pittsburgh, Pittsburgh, PA (United States)
Publication Date:
OSTI Identifier:
1333084
Grant/Contract Number:
AC05-00OR22725
Type:
Accepted Manuscript
Journal Name:
Molecular BioSystems
Additional Journal Information:
Journal Volume: 12; Journal Issue: 12; Journal ID: ISSN 1742-206X
Publisher:
Royal Society of Chemistry
Research Org:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source
Sponsoring Org:
ORNL LDRD Director's R&D; USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES