title: Age-dependent deamidation of glutamine residues in human γS crystallin: deamidation and unstructured regions.
abstract: Human aging is associated with the deterioration of long-lived proteins. Gradual cumulative modifications to the life-long proteins of the lens may ultimately be responsible for the pronounced alterations to the optical and physical properties that characterize lenses from older people. γS 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. Deamidation 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. Gln92 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 γS crystallin, showed a similar deamidation profile to that of Gln92. As the other Gln residues in β-sheet regions of γS crystallin appear to remain as amides, modification of Gln92 and Gln170 thus conforms to a pattern whereby deamidation is localized to the unstructured regions of long-lived proteins.
authors.affiliation: Save Sight Institute, Sydney Eye Hospital, University of Sydney, Sydney, New South Wales 2000, Australia.
authors.forename: Michelle Yu Sung
authors.initials: MY
authors.lastname: Hooi
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Roger John Willis
authors.initials: RJ
authors.lastname: Truscott
mesh_terms: D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D000375:Aging; D000577:Amides / Q000032:analysis; D000595:Amino Acid Sequence; D002386:Cataract / Q000378:metabolism; D002648:Child; D005973:Glutamine / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism; D008875:Middle Aged; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D055815:Young Adult; D038222:gamma-Crystallins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000577:Amides; D038222:gamma-Crystallins; D005973:Glutamine; C077648:CRYGS protein, human