The eye lens chaperone α-crystallin forms defined globular assemblies

α-Crystallins are molecular chaperones that protect vertebrate eye lens proteins from detrimental protein aggregation. αB-Crystallin, 1 of the 2 α-crystallin isoforms, is also associated with myopathies and neuropathological diseases. Despite the importance of α-crystallins in protein homeostasis, only little is known about their quaternary structures because of their seemingly polydisperse nature. Here, we analyzed the structures of recombinant α-crystallins using biophysical methods. In contrast to previous reports, we show that αB-crystallin assembles into defined oligomers consisting of 24 subunits. The 3-dimensional (3D) reconstruction of αB-crystallin by electron microscopy reveals a sphere-like structure with large openings to the interior of the protein. αA-Crystallin forms, in addition to complexes of 24 subunits, also smaller oligomers and large clusters consisting of individual oligomers. This propensity might explain the previously reported polydisperse nature of α-crystallin.

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