The IXI/V motif in the C-terminal extension of alpha-crystallins: alternative interactions and oligomeric assemblies.

Purpose: Alpha-crystallin, a hetero-oligomer of alphaA- and alphaB-crystallin, is involved in maintaining eye lens transparency, primarily by its structural packing and chaperone activity. alphaA- and alphaB-crystallin share significant sequence homology, which is almost exclusively restricted to the central, conserved "alphaA-crystallin domain". The flanking N-terminal domain and C-terminal extension are highly variable both in sequence and length.

Role of the conserved SRLFDQFFG region of alpha-crystallin, a small heat shock protein. Effect on oligomeric size, subunit exchange, and chaperone-like activity.

Small heat shock proteins (sHsps) are necessary for several cellular functions and in stress tolerance. Most sHsps are oligomers; intersubunit interactions leading to changes in oligomeric structure and exposure of specific regions may modulate their functioning. Many sHsps, including alpha A- and alpha B-crystallin, contain a well conserved SRLFDQFFG sequence motif in the N-terminal region.

Role of the C-terminal extensions of alpha-crystallins. Swapping the C-terminal extension of alpha-crystallin to alphaB-crystallin results in enhanced chaperone activity.

Several small heat shock proteins contain a well conserved alpha-crystallin domain, flanked by an N-terminal domain and a C-terminal extension, both of which vary in length and sequence. The structural and functional role of the C-terminal extension of small heat shock proteins, particularly of alphaA- and alphaB-crystallins, is not well understood. We have swapped the C-terminal extensions between alphaA- and alphaB-crystallins and generated two novel chimeric proteins, alphaABc and alphaBAc.