How hydrophobicity, side chains, and salt affect the dimensions of disordered proteins
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Understanding the driving forces behind stability of denatured state ensembles (DSE’s) and intrinsically disordered proteins (IDP’s) is central to a number of unresolved questions in bimolecular thermodynamics regarding protein folding pathways and foldability, thermodynamic stability, aggregation and misfolding. Researchers at the University of Chicago and Notre Dame used temperature-controlled size-exclusion chromatography-coupled SAXS (SEC-SAXS) and NMR to examine how temperature and solvent ionic strength influences the solution structure(s) of the N-terminal domain of pertactin (PNt). PNt is a valuable model system from a fundamental biophysical point of view, as the full-length 539-residue pertactin folds into a parallel β-helix but the 334 N-terminal residues do not and instead behave as a highly expanded, intrinsically disordered chain.
In this work, the authors used temperature-series SEC-SAXS experiments performed at BioCAT, with temperatures ranging from 4 to 60 degrees C, to show that PNt displays a mild, temperature-dependent contraction (as measured by Rg value). Glycine-rich low hydrophobicity model systems (as proxies for protein backbones alone) did not display an analogous trend, showing the specific importance of side chain interactions. Increasing the ionic strength of the …