Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor

Caleb B. McDonald, Vikas Bhat, Dmitry Kurouski, David C. Mikles, Brian J. Deegan, Kenneth L. Seldeen, Igor K. Lednev, Amjad Farooq

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)54-62
Number of pages9
JournalBiophysical Chemistry
Volume175-176
DOIs
StatePublished - May 1 2013

Fingerprint

Proline
Nucleotides
Conformations
Intrinsically Disordered Proteins
Cell signaling
Guanine Nucleotide Exchange Factors
Denaturation
Cerebral Palsy
Hydrodynamics
Health
Molecules

Keywords

  • Proline-rich proteins Structural disorder Random coil Polyproline II helices Conformational dynamics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Organic Chemistry

Cite this

McDonald, C. B., Bhat, V., Kurouski, D., Mikles, D. C., Deegan, B. J., Seldeen, K. L., ... Farooq, A. (2013). Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor. Biophysical Chemistry, 175-176, 54-62. https://doi.org/10.1016/j.bpc.2013.02.008

Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor. / McDonald, Caleb B.; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C.; Deegan, Brian J.; Seldeen, Kenneth L.; Lednev, Igor K.; Farooq, Amjad.

In: Biophysical Chemistry, Vol. 175-176, 01.05.2013, p. 54-62.

Research output: Contribution to journalArticle

McDonald, CB, Bhat, V, Kurouski, D, Mikles, DC, Deegan, BJ, Seldeen, KL, Lednev, IK & Farooq, A 2013, 'Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor', Biophysical Chemistry, vol. 175-176, pp. 54-62. https://doi.org/10.1016/j.bpc.2013.02.008
McDonald CB, Bhat V, Kurouski D, Mikles DC, Deegan BJ, Seldeen KL et al. Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor. Biophysical Chemistry. 2013 May 1;175-176:54-62. https://doi.org/10.1016/j.bpc.2013.02.008
McDonald, Caleb B. ; Bhat, Vikas ; Kurouski, Dmitry ; Mikles, David C. ; Deegan, Brian J. ; Seldeen, Kenneth L. ; Lednev, Igor K. ; Farooq, Amjad. / Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor. In: Biophysical Chemistry. 2013 ; Vol. 175-176. pp. 54-62.
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