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Asp isomerization increases aggregation of α-crystallin and decreases its chaperone activity in human lens of various ages.
- Source :
-
Biochimica et biophysica acta. Proteins and proteomics [Biochim Biophys Acta Proteins Proteom] 2020 Sep; Vol. 1868 (9), pp. 140446. Date of Electronic Publication: 2020 May 19. - Publication Year :
- 2020
-
Abstract
- α-Crystallin, comprising 40-50 subunits of αA- and αB-subunits, is a long-lived major soluble chaperone protein in lens. During aging, α-crystallin forms aggregates of high molecular weight (HMW) protein and eventually becomes water-insoluble (WI). Isomerization of Asp in α-crystallin has been proposed as a trigger of protein aggregation, ultimately leading to cataract formation. Here, we have investigated the relationship between protein aggregation and Asp isomerization of αA-crystallin by a series of analyses of the soluble α-crystallin, HMW and WI fractions from human lens samples of different ages (10-76 years). Analytical ultracentrifugation showed that the HMW fraction had a peak sedimentation coefficient of 40 S and a wide distribution of values (10-450 S) for lens of all ages, whereas the α-crystallin had a much smaller peak sedimentation coefficient (10-20 S) and was less heterogeneous, regardless of lens age. Measurement of the ratio of isomers (Lα-, Lβ-, Dα-, Dβ-) at Asp58, Asp91/92 and Asp151 in αA-crystallin by liquid chromatography-mass spectrometry showed that the proportion of isomers at all three sites increased in order of aggregation level (α-crystallin < HMW < WI fractions). Among the abnormal isomers of Asp58 and Asp151, Dβ-isomers were predominant with a very few exceptions. Notably, the chaperone activity of HMW protein was minimal for lens of all ages, whereas that of α-crystallin decreased with increasing lens age. Thus, abnormal aggregation caused by Asp isomerization might contribute to the loss of chaperone activity of α-crystallin in aged human lens.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Aging metabolism
Child
Chromatography, High Pressure Liquid
Crystallins
Humans
Isomerism
Lens, Crystalline metabolism
Mass Spectrometry
Middle Aged
Molecular Weight
Young Adult
alpha-Crystallins metabolism
Cataract metabolism
Lens, Crystalline chemistry
Protein Aggregation, Pathological metabolism
alpha-Crystallins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1454
- Volume :
- 1868
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Proteins and proteomics
- Publication Type :
- Academic Journal
- Accession number :
- 32442520
- Full Text :
- https://doi.org/10.1016/j.bbapap.2020.140446