FC0014
αA-crystallin  -  high molecular mass (HMM) complexes with insulin, α-lactalbumin ovotransferrin

Biological function
α-crystallin belongs to the family of small heat shock proteins. It forms a dynamic multimeric complex of two subunits in eye lens.

Structural evidence
Most of the protein forms β-sheets, with a disordered C-terminal extension. NMR data show that upon chaperone activity, α- crystallin does not undergo gross structural alterations: it largely retains flexibility of the C terminal part even in complex with its substrates (it is only in αΑ and not in αΒ subunit).

Biochemical evidence
The disordered C-terminal extension has impact on the chaperone activity. Increasing hydrophobicity of the C terminal extension, by even inserting one tryptophane residue greatly diminishes ability to prevent aggregation of insulin B-chains. Increasing chaperone activity is related to exposure of more hydrophobic residues in the C terminal region.

Structure/Mechanism
The maintenance of C-terminal flexibility in αA-crystallin, and at least partially in the αB-crystallin, during chaperone action and formation of the HMM complex suggests that flexibility in this region is required for solubilisation in α-crystallin prior to, and after, formation of the HMM (high molecular mass) complex. It places the C-terminal extensions at both ends of an annular arrangement, which would allow for a large region of exposed hydrophobicity that is sufficiently spatially separated from the flexible extensions to enable interactions with the substrate protein without affecting the flexibility of the terminal extensions of αΑ-crystallin.

Mechanism category
tethering

Significance
The disordered C-terminal tail is required for solubilisation of αΑ-crystallin and enable hydrophobic regions to be exposed to interact with the substrate.