Species-Specific Structural and Functional Divergence of ?-Crystallins: Zebrafish ?Ba- and Rodent ?A(ins)-Crystallin Encode Activated Chaperones.

ABSTRACT: In addition to contributing to lens optical properties, the ?-crystallins are small heat shock proteins that possess chaperone activity and are predicted to bind and sequester destabilized proteins to delay cataract formation. The current model of ?-crystallin chaperone mechanism envisions a transition from the native oligomer to an activated form that has higher affinity to non-native states of the substrate. Previous studies have suggested that this oligomeric plasticity is encoded in the primary sequence and controls access to high affinity binding sites within the N-terminal domain. Here, we further examined the role of sequence variation in the context of species-specific ?-crystallins from rat and zebrafish. Alternative splicing of the ?A gene in rodents produces ?A(ins), which is distinguished by a longer N-terminal domain. The zebrafish genome includes duplicate ?B-crystallin genes, ?Ba and ?Bb, which display divergent primary sequence and tissue expression patterns. Equilibrium binding experiments were employed to quantitatively define chaperone interactions with a destabilized model substrate, T4 lysozyme. In combination with multiangle light scattering, we show that rat ?A(ins) and zebrafish ?-crystallins display distinct global structural properties and chaperone activities. Notably, we find that ?A(ins) and ?Ba demonstrate substantially enhanced chaperone function relative to other ?-crystallins, binding the same substrate more than 2 orders of magnitude higher affinity and mimicking the activity of fully activated mammalian small heat shock proteins. These results emphasize the role of sequence divergence as an evolutionary strategy to tune chaperone function to the requirements of the tissues and organisms in which they are expressed.

SUBMITTER: Koteiche HA 

PROVIDER: S-EPMC5240591 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature