利用定點突變探討具有分子保護者活性的豬和魚類-水晶體蛋白的結構－活性相關性

Crystallins in the eyes would loss their structural stability and then aggregate
because of UV damage, glycation, and oxidation during lifespan. Crystallin
aggregation might be a major cause to cataract formation. α-Crystallin, a major
protein of all vertebrate lenses (about 30%), consisting of two subunits αA and αB,
could prevent other crystallin aggregations by its chaperone-like activity. It suggested
that the chaperone-like activity of α-crystallin might be related to the cataract
formation during aging. αB-crystallin, one subunit of α-crystallin, could be found in
heart and muscle and other tissues. αB-crystallin was found to be functionally related
to the stability of cytoskeletons, especially with intermediate filaments. In our
previous studies, we cloned and expressed the recombinant αB-crystallins from
porcine and catfish. The comparison studies were focused on the structural stability,
chaperone-like activity, and other biophysical characteristics. We tried to explain the
dependence of functional differences on structure. These results have been published.
In this study, we have constructed the conserved domains chimeric mutants to explore
the structure-function relationship directly. These results indicated that the
determinant of functional differences was the α-crystallin domain, the most conserved
domain in small heat shock protein family. The further studies on a-crystallin domain
might give us detail mechanism of α-crystallin chaperone-like activity.