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

Abstract

\Crystallins are small heat-shock proteins that act as holdase chaperones. In humans, \-crystallin is expressed only in the eye lens, while \-crystallin is found in many tissues. \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. \-Crystallin prevents aggregation of damaged beta? and gamma?crystallins by binding to the client protein using a variety of binding modes. \-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, \-crystallins are particularly amenable to structure determination by solid-state nuclear magnetic resonance (NMR) and solution NMR, as well as cryo-electron microscopy.