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[摘要]：The small heat-shock protein alpha-crystallin isolated from the eye lens exists as a large (700 kDa) heteropolymer composed of two subunits, alpha A and alpha B, of 20 kDa each. Although trace amounts of alpha A-crystallin are found in other tissues, non-lenticular distribution of alpha-crystallin is dominated by the aB homopolymer. In most vertebrate lens, the molar ratio of alpha A to alpha B is generally 3: 1. However, the importance of this ratio in the eye lens is not known. In the present Study, we have investigated the physiological significance of the 3:1 ratio by determining the secondary/tertiary structure, hydrophobicity and chaperone-like activity of alpha A and alpha B-homopolymers and heteropolymers with different ratios of alpha A to aB subunits. Although, under physiologically relevant conditions, the alpha B-homopolymer (37-40 degrees C) has shown relatively higher activity, the alpha A-homopolymer or the heteropolymer with a higher alpha A proportion (3:1 ratio) has shown greater chaperone-like activity at elevated temperatures (> 50 degrees C) and also upon structural perturbation. Furthermore, higher-chaperone activity at elevated temperatures as well as upon structural perturbation is mainly mediated through increased hydrophobicity of alpha A. Although homopolymers and heteropolymers of a-crystallin (lid not differ in their secondary structure, changes in tertiary structure due to structural perturbations upon pre-heating are mediated predominantly by alpha A. Interestingly, the heteropolymer with higher alpha A proportion (3: 1) or the alpha A-homopolymer seems to be better chaperones in protecting lens beta- and gamma-crystallins at both normal and elevated temperatures. Thus lens might have favoured a combination of these qualities to achieve optimal protection under both native and stress (perturbed) conditions for which the heteropolymer with alpha A to alpha B in the 3:1 ratio appears to be better suited. |
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