alpha-Crystallins in the Vertebrate Eye Lens: Complex Oligomers and Molecular Chaperones

alpha-Crystallins are small heat-shock proteins that act as holdase chaperones. In humans, alpha A-crystallin is expressed only in the eye lens, while alpha B-crystallin is found in many tissues. alpha-Crystallins have a central domain flanked by flexible extensions and form dynamic, heterogeneous oligomers. Structural models show that both the C- and N-terminal extensions are important for controlling oligomerization through domain swapping. alpha-Crystallin prevents aggregation of damaged beta- and gamma-crystallins by binding to the client protein using a variety of binding modes. alpha-Crystallin chaperone activity can be compromised by mutation or posttranslational modifications, leading to protein aggregation and cataract. Because of their high solubility and their ability to form large, functional oligomers, alpha-crystallins are particularly amenable to structure determination by solid-state nuclear magnetic resonance (NMR) and solution NMR, as well as cryo-electron microscopy.

Automated summary

Alpha-crystallins are small heat-shock proteins acting as holdase chaperones with the ability to prevent aggregation of damaged crystallins. They form dynamic, heterogeneous oligomers with central domains flanked by flexible extensions, and control oligomerization through domain swapping. Mutations or modifications can compromise their chaperone activity, leading to protein aggregation and cataract formation.