Tobin Sosnick

Tobin Sosnick

Department Chair
University of Chicago
Chicago, IL


SAXS Finds that Water is a Good Solvent for Many Disordered Proteins but the Addition of FRET Fluorophores can Alter this Property

The dimensions that unfolded and intrinsically disordered proteins, IDPs, adopt at low or no denaturant remains controversial. We recently developed an analysis procedure for small-angle X-ray scattering, SAXS, and found that even relatively hydrophobic IDPs remain nearly as expanded as the chemically denatured ensemble, Riback et al., Science 2017.


Hence, water should be considered a good solvent for most unfolded states and an early collapse phase in not obligatory in the folding of many proteins. In contrast, FRET studies, and simulations, often find disordered conformations to be compact. We achieve reconciliation by showing that the addition of FRET fluorophores reduces the disordered protein’s dimensions.

We also tested the suggestion that FRET and SAXS results can be reconciled if the Rgyration and Rend-to-end are "uncoupled," i.e., no longer proportional, unlike random walk homopolymers. We find, however, that these two measures remain proportional.

We conclude that mild chain contraction and fluorophore-based interactions, along with improved analysis procedures for both SAXS and FRET, can explain the preponderance of existing data regarding the dimensions of unfolded polypeptides. We propose that having disordered and unfolded proteins be solvated and expanded is biologically beneficial as these properties reduce unwanted misfolding and aggregation in vivo.


Joshua A Riback a , Micayla A Bowman b, Adam M Zmyslowski c, Kevin W Plaxco d, Patricia L Clark b*, Tobin R Sosnick c*


a Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637
b Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556
c Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637
d Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106

Lecture Images

Tobin Sosnick presenting at APS2019 Tobin Sosnick presenting at APS2019 Tobin Sosnick presenting at APS2019