Cooperative motion and hydrogen exchange stability in protein β-sheets

Abstract

Protein molecules are dynamical structures due to the continual exchange of thermal energy between them and the solvent environment^1,2. This dynamic behaviour is manifest in hydrogen exchange experiments, which reflect transient solvent accessibility of groups usually buried in the protein interior^3,4. However, studies of hydrogen exchange kinetics in pancreatic trypsin inhibitor (PTI) reveal a small subset of amide protons which exchange very slowly^5,6. Four of these groups form successive interchain hydrogen bonds in the central region of an antiparallel β-sheet⁷ (Fig. 1). Here I suggest that the unusual exchange stability of these β-sheet protons reflects the structure's intrinsic flexibility. This property allows transient energy fluctuations to be accommodated as cooperative motions which do not locally strain the interchain hydrogen bonds.