We have investigated the effect of nonenzymatic glycation (fructation) in vitro on the structure and stability of two proteins that are glycated in vivo as a consequence of high endogenous levels of sugar. We find that whereas fructation leads to the structural destabilization of the monomeric gamma-crystallin from the core of the eye lens, it leads to an increase in stability in the multimeric alpha-crystallin of the lens cortex. Thus, while glycated gamma-crystallin shows (a) a longer wavelength of fluorescent emission, indicating a greater exposure of its aromatic side chains to the medium; (b) a reduced secondary structural content; and (c) a more facile denaturation by thermodynamic and chemical means, alpha-crystallin displays the opposite behavior. Furthermore, alpha-crystallin shows an increased tendency toward multimeric aggregation upon fructation. We interpret these differences in the broad context of the effects of neutralization of positive charges on protein structure and stability. Fructation tends to destabilize gamma-crystallin, by effecting a significant reversal in the balance of charges in the protein, at physiological pH. alpha-Crystallin is a multimeric protein whose pI is lower than its pH of optimum stability. Fructation in this case effectively neutralizes the cationic charges and promotes conformational order. This study indicates that although glycation brings about similar changes in the covalent chemical structures of proteins, its influence on the three-dimensional structures of different proteins can be different.
Nonenzymatic glycation alters protein structure and stability. A study of two eye lens crystallins.
Published 1993 in Journal of Biological Chemistry
ABSTRACT
PUBLICATION RECORD
- Publication year
1993
- Venue
Journal of Biological Chemistry
- Publication date
1993-08-25
- Fields of study
Biology, Medicine, Chemistry
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- alpha-crystallin
A multimeric eye-lens crystallin protein from the lens cortex used as the second protein examined.
Aliases: alpha crystallin
- gamma-crystallin
A monomeric eye-lens crystallin protein from the lens core used as one of the two proteins examined.
Aliases: gamma crystallin
- multimeric aggregation
The association of multiple protein subunits into larger multimeric assemblies.
Aliases: aggregation
- neutralization of positive charges
The reduction of cationic charge on protein residues discussed as a context for altered protein behavior after glycation.
Aliases: charge neutralization
- nonenzymatic glycation
A sugar-driven covalent modification of proteins examined here through fructose-derived glycation chemistry.
Aliases: fructation
- protein stability
A protein's resistance to unfolding or denaturation under thermal or chemical stress in the assay conditions.
- protein structure
The three-dimensional and secondary-structure organization of a protein analyzed in the glycation experiments.
REFERENCES
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