Alpha B- and beta A3-crystallins containing D-Aspartic acids exist in a monomeric state

作者：Sakaue Hiroaki; Takata Takumi; Fujii Norihiko; Sasaki Hiroshi; Fujii Noriko

来源：Biochimica et Biophysica Acta-Proteins and Proteomics, 2015, 1854(1): 1-9.

DOI：10.1016/j.bbapap.2014.10.006

• Racemization
• Monomerization
• D-Asp
• alpha B-crystallin
• beta A3-crystallin

Crystallin stability and subunit-subunit interaction are essential for eye lens transparency. There are three types of crystallins in lens, designated as alpha-, beta-, and gamma-crystallins. Alpha-crystallin is a hetero-polymer of about 800 kDa, consisting of 35-40 subunits of two different alpha A- and alpha B-subunits, each of 20 kDa.The beta/gamma-crystallin superfamily comprises oligomeric beta-crystallin (2-6 subunits) and monomeric gamma-clystallin. Since lens proteins have very long half-lives, they undergo numerous post-translational modifications including racemization, isomerization, deamidation, oxidation, glycation, and truncation, which may decrease crystallin solubility and ultimately cause cataract formation. Racemization and isomerization of aspartyl (Asp) residues have been detected only in polymeric a- and oligomeric beta-crystallin, while the situation in monomeric gamma-clystallin has not been studied. Here, we investigated the racemization and isomerization of Asp in the gamma-crystallin fraction of elderly donors. The results show that Asp residues of gamma S-, gamma 1D- and gamma C-crystallins were not racemized and isomerized. However, strikingly, we found that a portion of aB-crystallin and SA3-crystallin moved to the lower molecular weight fraction which is the same size of y-crystallin. In those fractions, Asp-96 of alpha B-crystallin and Asp-37 of beta A3-crystallin were highly inverted, which do not occur in the native lens higher molecular weight fraction. Our results indicate the possibility that the inversion of Asp residues may induce dissociation of (alpha B- and beta A3-crystallins from the polymeric and oligomeric states. This is the first report that stereoinversion of amino acids disturbs lens protein assembly in aged human lens.

• 出版日期2015-1