To Exchange or Not to Exchange? That is the question — at least for the graduate students participating in our Proteins Journal Club this semester (my apologies to those members of the Shakespearean Journal Club — although I do like the musical version of Hamlet as performed on Gilligan’s Island).
The propensity of an amide proton of an amino acid residue of a protein to deuterium exchange is related to its hydrogen bonding environment. If the amide proton is participating in a strong hydrogen bond with a carbonyl oxygen as occurs in an alpha-helix or beta-sheet, it will be more difficult to exchange with a deuteron than an amide proton that is part of a loop or a region of a protein that has a high degree of flexibility and exposure to solvent (Figure 1). The sites of exchange can be monitored by NMR or mass spectrometry analysis, thus allowing protein folding and structural dynamics to be measured by the accumulation of deuterium.