Calcium-induced decrease of the thermal stability and chaperone activity of alpha-crystallin.
Biochim Biophys Acta
; 1601(1): 100-9, 2002 Nov 19.
Article
en En
| MEDLINE
| ID: mdl-12429508
Alpha-crystallin, one of the major proteins in the vertebrate eye lens, acts as a molecular chaperone, like the small heat-shock proteins, by protecting other proteins from denaturing under stress or high temperature conditions. alpha-Crystallin aggregation is involved in lens opacification, and high [Ca(2+)] has been associated with cataract formation, suggesting a role for this cation in the pathological process. We have investigated the effect of Ca(2+) on the thermal stability of alpha-crystallin by UV and Fourier-transform infrared (FTIR) spectroscopies. In both cases, a Ca(2+)-induced decrease in the midpoint of the thermal transition is detected. The presence of high [Ca(2+)] results also in a marked decrease of its chaperone activity in an insulin-aggregation assay. Furthermore, high Ca(2+) concentration decreases Cys reactivity towards a sulfhydryl reagent. The results obtained from the spectroscopic analysis, and confirmed by circular dichroism (CD) measurements, indicate that Ca(2+) decreases both secondary and tertiary-quaternary structure stability of alpha-crystallin. This process is accompanied by partial unfolding of the protein and a clear decrease in its chaperone activity. It is concluded that Ca(2+) alters the structural stability of alpha-crystallin, resulting in impaired chaperone function and a lower protective ability towards other lens proteins. Thus, alpha-crystallin aggregation facilitated by Ca(2+) would play a role in the progressive loss of transparency of the eye lens in the cataractogenic process.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcio
/
Alfa-Cristalinas
Límite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2002
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Países Bajos