title: Simultaneous stereoinversion and isomerization at the Asp-4 residue in βB2-crystallin from the aged human eye lenses.
abstract: The lens proteins are composed of α-, β-, and γ-crystallins that interact with each other to maintain the transparency and refractive power of the lens. Because the lens crystallins are long-lived proteins, they undergo various post-translational modifications including racemization, isomerization, deamidation, oxidation, glycation, and truncation. In βB2-crystallin, which is the most abundant β-crystallin, the deamidation of asparagine and glutamine residues has been reported. Here, we found that the aspartyl (Asp) residue at position 4 of βB2-crystallin in the lenses of elderly human individuals undergoes a significant degree of inversion and isomerization to the biologically uncommon residue D-β-Asp. Surprisingly, the D/L ratio of β-Asp at position 4 in βB2-crystallin from elderly donors (67-77 year old) was 0.88-3.21. A D/L ratio of amino acids greater than 1.0 is defined as an inversion of configuration from the L- to D-form, rather than a racemization. These extremely high D/L ratios are equivalent to those of Asp-58 and Asp-151 (D/L ratio: 3.1 for Asp-58 and 5.7 for Asp-151) in αA-crystallin from elderly donors (~80 year old) as reported previously. Initially, we identified specific Asp residues in the β-crystallin family of proteins that undergo a high degree of inversion. These results show that the isomerization and inversion of Asp residues occurs both in the α- and β-crystallins of the lens. Inversion of these Asp residues directly affects the higher order structure of the protein. Hence, this modification may change crystallin-crystallin interactions and disrupt the function of crystallins in the lens.
authors.affiliation: Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Fujii
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Fujii
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002386:Cataract / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007536:Isomerism; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D013237:Stereoisomerism; D038206:beta-Crystallin B Chain / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2; D001216:Asparagine