Nonenzymatic glycation alters protein structure and stability. A study of two eye lens crystallins.


Abstract

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. Study holds ProTherm entries: 5219, 5220, 5221 Extra Details: control gamma nonenzymatic glycation; structural destabilization;,aromatic side chains; secondary structural content; aggregation

Submission Details

ID: u3mSXJec3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:29 p.m.

Version: 1

Publication Details
Luthra M;Balasubramanian D,J. Biol. Chem. (1993) Nonenzymatic glycation alters protein structure and stability. A study of two eye lens crystallins. PMID:8349689
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1AMM 1996-11-08 1.2 1.2 ANGSTROM STRUCTURE OF GAMMA-B CRYSTALLIN AT 150K
4W9B 2015-09-09 1.28 Crystal structure of Gamma-B Crystallin expressed in E. coli based on mRNA variant 1
4W9A 2015-09-09 1.38 Crystal structure of Gamma-B Crystallin expressed in E. coli based on mRNA variant 2
4GCR 1993-10-31 1.47 STRUCTURE OF THE BOVINE EYE LENS PROTEIN GAMMA-B (GAMMA-II)-CRYSTALLIN AT 1.47 ANGSTROMS
1DSL 1996-07-11 1.55 GAMMA B CRYSTALLIN C-TERMINAL DOMAIN
1GCS 1994-04-30 2.0 STRUCTURE OF THE BOVINE GAMMA-B CRYSTALLIN AT 150K
1I5I 2001-03-07 2.4 THE C18S MUTANT OF BOVINE (GAMMA-B)-CRYSTALLIN
1GAM 1996-07-11 2.6 GAMMA B CRYSTALLIN TRUNCATED C-TERMINAL DOMAIN

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
92.0 Gamma-crystallin B P10066 CRGB_RAT
94.9 Gamma-crystallin B A3RLE1 CRGB_CANLF
100.0 Gamma-crystallin B P02526 CRGB_BOVIN