Anion-Facilitated Hydrogen–Deuterium Exchange as a Tool to Probe Weak Anion–Protein Interactions Responsible for Hofmeister Effects

• DOI: 10.1021/acs.jpcb.4c08619
• Publication Date: 2025-02-13T16:00:10Z
• Authors: Thien H. Tran; Meghan Ricciardi; Lilly I. Grunski; William C. Wimley; Marcey L. Waters; Bruce C. Gibb
• Keywords: Hydrogen–deuterium exchange; Hofmeister series

Impeded by the complexity of proteinaceous structure and very weak nature noncovalent interactions involved, detailed mechanisms which anions induce salting-in Hofmeister effects in proteins peptides remain unclear. Here, using β-hairpin as models, we examine two approaches to qualify (map) anion binding: 1H NMR chemical shifts hydronium-catalyzed hydrogen–deuterium exchange (HDX) rate changes. We demonstrate that each salt investigated─despite an affinity too quantify accurately, caused denaturation extent is both peptide anion-specific, with more charge-diffuse inducing a greater degree unfolding. Our studies reveal HDX mapping provides detail than shift data. Thus, reveals slightly different denaturation, depending on anion. Namely, assisted N-terminal Arg residue, charge-dense Cl– chelated terminal N–H groups hairpin induces small whereas intercalate deeply into cation-π-hydrophobic core substantial These findings provide glimpse can effect suggest useful tool map binding.