Journal
BIOPHYSICAL CHEMISTRY
Volume 175, Issue -, Pages 54-62Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bpc.2013.02.008
Keywords
Proline-rich proteins; Structural disorder; Random coil; Polyproline II helices; Conformational dynamics
Funding
- National Institutes of Health [R01-GM083897, R01-AG033719, T32-CA119929]
- USylvester Braman Family Breast Cancer Institute
- US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-98CH10886]
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Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. (C) 2013 Elsevier B.V. All rights reserved.
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