title: Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor.
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.
authors.affiliation: Department of Biochemistry & Molecular Biology, Leonard Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Caleb B
authors.initials: CB
authors.lastname: McDonald
authors.forename: Vikas
authors.initials: V
authors.lastname: Bhat
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kurouski
authors.forename: David C
authors.initials: DC
authors.lastname: Mikles
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Deegan
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Seldeen
authors.forename: Igor K
authors.initials: IK
authors.lastname: Lednev
authors.forename: Amjad
authors.initials: A
authors.lastname: Farooq
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019791:Guanidine / Q000737:chemistry; D006801:Humans; D008027:Light; D008969:Molecular Sequence Data; D011392:Proline / Q000737:chemistry*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D020837:SOS1 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012542:Scattering, Radiation; D014508:Urea / Q000737:chemistry
chemical_list: D011994:Recombinant Proteins; D020837:SOS1 Protein; D014508:Urea; D011392:Proline; D019791:Guanidine