| Autor: |
Sinha, Debasish, Wyatt, M. Keith, Sarra, Robert, Jaworski, Cynthia, Slingsby, Christine, Thaung, Caroline, Pannell, Lewis, Robison, W. Gerald, Favor, Jack, Lyon, Mary, Wistow, Graeme |
| Zdroj: |
Journal of Biological Chemistry; March 2001, Vol. 276 Issue: 12 p9308-9315, 8p |
| Abstrakt: |
In Opj, an inherited cataract in mice, opacity is associated with a mutation in Crygs, the gene for γS-crystallin, the first mutation to be associated with this gene. A single base change causes replacement of Phe-9, a key hydrophobic residue in the core of the N-terminal domain, by serine. Despite this highly non-conservative change, mutant protein folds normally at low temperature. However, it exhibits a marked, concentration-dependent decrease in solubility, associated with loss of secondary structure, at close to physiological temperatures. This is reminiscent of processes thought to occur in human senile cataracts in which normal proteins become altered and aggregate. The Opjcataract is progressive and more severe in Opj/Opjthan in Opj/+. Lens histology shows that whereas fiber cell morphology in Opj/+mice is essentially normal, in Opj/Opj, cortical fiber cell morphology and the loss of maturing fiber cell nuclei are both severely disrupted from early stages. This may indicate a loss of function of γS-crystallin which would be consistent with ideas that members of the βγ-crystallin superfamily may have roles associated with maintenance of cytoarchitecture. |
| Databáze: |
Supplemental Index |
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