Age-dependent deamidation of glutamine residues in human crystallin: deamidation and unstructured regions
Human aging is associated with the deterioration of long-lived proteins. Gradual cumu ative modifications to the life-long proteins of the [ens may ultimately be responsible for the pronounced alterations to the optical and physical properties that characterize lenses from older people . ..,S crystallin, a major human lens protein, is known to undergo several age-dependent changes. Using proteomic techniques, a site of deamidation involving glutamine 92 has been characterized and its time course established. The proportion of deamidation increased from birth to teen-age years and then plateaud. Ceamidation at this site increased again in the eighth decade of life. There was no significant difference in the extent of deamidation between cataract and age-matched normal lenses. Glng2 is located in the linker region between the two domains, and the introduction of a negative charge at this site may alter the interaction between the two regions of the protein. Gln170, which is located in another unstructured part of ..,S crystallin, showed a similar deamidation profile to that of Gln92. As the other Gin residues in p-sheet regions of ..,S crystallin appear to remain as amides, modification of Gln92 and Gln170 thus conforms to a pattem whereby deamidation is localized to the unstructured regions of long-lived proteins.