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Intrapolypeptide disulfides in human alphaA-crystallin and their effect on chaperone-like function
M Cherian-Shaw1, J B Smith, X Y Jiang
1Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100, USA.
Molecular and Cellular Biochemistry
|November 2, 1999
Summary
Aging causes a loss in alpha-crystallin chaperone activity due to protein-protein disulfides (PSSP). Restoring disulfide bonds with glutathione reductase (GR) improved this function in human lenses.
Area of Science:
- Biochemistry
- Ophthalmology
- Aging Research
Background:
- Alpha-crystallins are crucial lens proteins with chaperone activity.
- Age-related changes in protein structure can impair protein function.
- Protein-protein disulfides (PSSP) are implicated in age-related protein dysfunction.
Purpose of the Study:
- To investigate the role of PSSP in the age-related decline of alpha-crystallin chaperone activity.
- To determine if disulfide bond reduction can restore chaperone function.
Main Methods:
- Isolation of alpha-crystallin from human lenses of varying ages.
- Assay of chaperone-like activity before and after glutathione reductase (GR) and NADPH treatment.
- Electrospray ionization mass spectrometry (ESIMS) to analyze protein structure and disulfide bond formation.
Main Results:
- Chaperone activity of alpha-crystallin decreased with age.
- GR treatment significantly improved the chaperone activity.
- ESIMS analysis indicated that intrapolypeptide disulfide bonds, particularly at Cys-131 and Cys-142 of alphaA-crystallin, increased with age.
Conclusions:
- Disulfide bond formation is a primary contributor to the age-dependent loss of alpha-crystallin chaperone activity in human lenses.
- Targeting disulfide bonds may offer therapeutic strategies for age-related vision impairment.