Age-related Asp Isomerizations in Lens Alpha-crystallin

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K16514
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Kyoto University (2016); Tokyo University of Pharmacy and Life Science (2015)
• Principal Investigator: Takata Takumi 京都大学, 原子炉実験所, 特定准教授 (80379007)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: D-アミノ酸 / クリスタリン / 白内障 / 加齢 / タンパク質異常凝集 / 質量分析

Outline of Final Research Achievements

The lens α-crystallin is composed of two subunits αA- and αB-crystallin (αA-Crys and αB-Crys), which form various oligomers and complexes. Recent studies have shown that many aspartyl residues (Asp) in αA-Crys inverted to isomers (Lβ-Asp, Dα-Asp, Dβ-Asp) with age. It has not been well understood whether Asp isomers in native polymeric αA-Crys are different from those in dissociated αA-Crys or those in aggregated complexes. We therefore examined to clarify the distribution of Asp isomers in dissociated αA-Crys and those in aggregated αA-Crys. The results showed that the isomerization of Asp 58 in αA-Crys were highly detectable from the monomeric fraction. In addition, age-dependent Asp 58 isomerization in α-Crys is similar to the ratio from lens insoluble fraction. The isomerization of Asp as well as many other modifications would reduce the normal subunit-subunit interaction of α-Crys with aging, result in senile cataract formation.

Free Research Field

生化学