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Investigating the Structure and Binding of Intrinsically Disordered Proteins
Author(s) -
DeBuhr Amanda Leilah,
Stanley Christopher,
Rowe Erica,
Grese Laura,
O'Neill Hugh,
Berthelier Valerie
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.909.5
Subject(s) - intrinsically disordered proteins , osmolyte , chemistry , folding (dsp implementation) , circular dichroism , biophysics , crystallography , biochemistry , biology , electrical engineering , engineering
Investigating the mechanism by which intrinsically disordered proteins (IDPs) acquire structure upon binding to their specific partners is technically challenging as the structural flexibility of IDPs limits the number of suitable techniques. We are using small‐angle neutron scattering (SANS) and circular dichroism (CD) spectroscopy coupled with osmotic stress to measure the conformational changes of two IDPs as related to their mutual binding. This binding pair, NCBD and ACTR, is a disordered region of CREB binding protein and its binding partner, respectively. Our obtained SANS structure on NCBD/ACTR complex is in good agreement with the NMR structure while SANS on ACTR reveals the expanded nature of the unbound, unfolded state. To more closely discern the folding properties of these IDPs, we also studied the influence of osmolytes on their conformation by CD spectroscopy. The osmotic stress applied by the presence of osmolytes revealed information on the hydration changes and energetics that accompany folding. This research presents new opportunities for studying the folding‐binding reactions of IDPs and overall yields insight into IDP function. This research is supported by a Laboratory Directed Research and Development (LDRD) grant from Oak Ridge National Laboratory, managed by UT‐Battelle for the Department of Energy.