As proteins age, they become damaged through the spontaneous racemization and isomerization of aspartic and asparaginyl residues. The accumulation of proteins with D- and isoAsp residues can result in loss of cell function. In previous work, we have shown that a primary way that cells deal with this damage is with a methylation cycle initiated by the PCMT1 methyltransferase. The action of this enzyme leads to the conversion of D-aspartyl residues to the L-configuration as well as the conversion of isopeptide linkages to normal peptide bonds. Such repair reactions may greatly increase the useful lifetime of cellular proteins and may help insure organismal survival. We have recently collaborated with Dr. Mark Mamula of Yale University to look at how the accumulation of isoaspartyl residues can generate new peptides for immune recognition and can lead to autoimmunological responses.

Publication: Yang, M.-L., Lam, T. T., Kanyo, J., Kang, I. Zhou, S. Z., Clarke, S. G. and Mamula, M. J. (2023) “Natural isoaspartyl modification of ZAP70 alters T cell responses in lupus” Autoimmunity Article 2282945. (https://doi.org/10.1080/08916934.2023.2282945).