RT Journal Article
SR Electronic
T1 The contribution of electrostatics to hydrogen exchange in the unfolded protein state
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.22.432104
DO 10.1101/2021.02.22.432104
A1 Rupashree Dass
A1 Enrico Corlianò
A1 Frans A. A. Mulder
YR 2021
UL http://biorxiv.org/content/early/2021/02/23/2021.02.22.432104.abstract
AB Although electrostatics have long been recognized to play an important role in hydrogen exchange (HX) with solvent, the quantitative assessment of its magnitude in the unfolded state has hitherto been lacking. This limits the utility of HX as a quantitative method to study protein stability, folding and dynamics. Using the intrinsically disordered human protein α-synuclein as a proxy for the unfolded state, we show that a hybrid mean-field approach can effectively compute the electrostatic potential at all backbone amide positions along the chain. From the electrochemical potential a fourfold reduction in hydroxide concentration near the protein backbone is predicted for the C-terminal domain, a prognosis that is in direct agreement with experimentally-derived protection factors from NMR spectroscopy. Thus, impeded HX for the C-terminal region of α-synuclein is not the result of intramolecular hydrogen bonding and/or structure formation.Competing Interest StatementThe authors have declared no competing interest.