Simultaneous stereoinversion and isomerization at specific aspartic acid residues in alpha A-crystallin from human lens.
We characterized the primary structure of alpha A-crystallin from the lens of the human eye by detailed analyses of the amino acid sequence, mass, and stereoisomers, and found the biologically uncommon D- and beta-aspartic acid (Asp) residues in the protein. The stereoconfiguration of the Asp151 and Asp58 residues in alpha A-crystallin from old subjects (mean age: 80 years) was inverted to the D-isomer, and the residues were simultaneously isomerized to beta-aspartyl residues, which may occur via a succinimide intermediate. This is thought to be the first observation of stereoinversion of amino acids in protein in vivo. It is noteworthy that similar stereoinversion was observed in the same residues of alpha A-crystallin from young subjects (age: 11 months), with simultaneous isomerization, although the extent of isomerization was low compared with that in the aged. The conversion may take place in the early life of the lens and the resulting isomers may accumulate with aging. We also found that terminal serine173 was cleaved in aged alpha A-crystallin. Since the cleavage was not observed in young alpha A-crystallin, it may result from the in vivo aging process. The present findings also make it necessary to revise the amino acid sequence of human alpha A-crystallin presented previously: human alpha A-crystallin is composed of 173 (formerly reported as 172) amino acid residues, and the sequence from residues 153 to 155 is THA (formerly reported as -HT).
Discovery Research Division, Takeda Chemical Industries, Ltd., Ibaraki.
N
N
Fujii
K
K
Satoh
K
K
Harada
Y
Y
Ishibashi
D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry*; D003459:Crystallins / Q000737:chemistry*; D006801:Humans; D007536:Isomerism; D007908:Lens, Crystalline / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D013237:Stereoisomerism; D013997:Time Factors
D003459:Crystallins; D001224:Aspartic Acid