Long-lived proteins may accumulate a range of modifications over time, including subtle alterations such as side-chain isomerization.

In collaboration with the
Julian group in UC Riverside and Benesch group in Oxford we study the effect of isomerisation of an aspartate residue in αB-crystallin, the most abundant chaperone proteins in the eye lens and within the longest-lived proteins in the body. Malfunction of these proteins is linked to a range of diseases, including cataract.

Our results illustrate how age-related isomerization of amino acid residues, which may seem to be only a minor structural perturbation, can disrupt native structural interactions with profound consequences for protein assembly and activity.

Lyon, Y.A., Collier, M.P., Riggs, D.L., Degiacomi, M.T., Benesch, J.L.P., Julian, R.R. (2019). Structural and functional consequences of age-related isomerization in α-crystallins, Journal of Biological Chemisty