Evolution of the alpha-crystallin/small heat-shock protein family.

Abstract

The common characteristic of the alpha-crystallin/small heat-shock protein family is the presence of a conserved homologous sequence of 90-100 residues. Apart from the vertebrate lens proteins--alpha A- and alpha B-crystallin--and the ubiquitous group of 15-30-kDa heat-shock proteins, this family also includes two mycobacterial surface antigens and a major egg antigen of Schistosoma mansoni. Multiple small heat-shock proteins are especially present in higher plants, where they can be distinguished in at least two classes of cytoplasmic proteins and a chloroplast-located class. The alpha-crystallins have recently been found in many tissues outside the lens, and alpha B-crystallin, in particular, behaves in many respects like a small heat-shock protein. The homologous sequences constitute the C-terminal halves of the proteins and probably represent a structural domain with a more variable C-terminal extension. These domains must be responsible for the common structural and functional properties of this protein family. Analysis of the phylogenetic tree and comparison of the biological properties of the various proteins in this family suggest the following scenario for its evolution: The primordial role of the small heat-shock protein family must have been to cope with the destabilizing effects of stressful conditions on cellular integrity. The alpha-crystallin-like domain appears to be very stable, which makes it suitable both as a surface antigen in parasitic organisms and as a long-living lens protein in vertebrates. It has recently been demonstrated that, like the other heat-shock proteins, the alpha-crystallins and small heat-shock proteins function as molecular chaperones, preventing undesired protein-protein interactions and assisting in refolding of denatured proteins. Many of the small heat-shock proteins are differentially expressed during normal development, and there is good evidence that they are involved in cytomorphological reorganizations and in degenerative diseases. In conjunction with the stabilizing, thermoprotective role of alpha-crystallins and small heat-shock proteins, they may also be involved in signal transduction. The reversible phosphorylation of these proteins appears to be important in this respect.

Characterization of Small HSPs from Anemonia viridis Reveals Insights into Molecular Evolution of Alpha Crystallin Genes among Cnidarians

“…Notably, none of the identified small HSPs contain a signal peptide or transmembrane domain. However, predictions of amphiphilic α-helices with a high hydrophobic moment in the N-termini of some small HSPs suggest that such structures may serve for insertion into membranes [47].…”

“…This motif was found in many of the sHSPs [47], [50], and it is involved in phosphorylation and oligomerisation, thus modulating the activity of ACD proteins.…”

A First Line of Stress Defense: Small Heat Shock Proteins and Their Function in Protein Homeostasis

“…A prominent group of these stress proteins are the molecular chaperones, which comprise several families classified according to their molecular mass and evolutionary history [2]. Small heat shock proteins (sHsps), which are present in all three domains of life, are the least conserved of the molecular chaperones [3, 4]. Among the most well-studied members of the sHsp family are the two α-crystallins, αA (or HspB4) and αB (or HspB5), which share 60% amino acid identity, and account for over 30% of protein in the vertebrate eye lens.…”

Site-Directed Mutations in the C-Terminal Extension of Human αB-Crystallin Affect Chaperone Function and Block Amyloid Fibril Formation

“…sHsps act specifically with target proteins that are on their off-folding pathway [9]. αB-Crystallin is primarily found in the eye lens, where it associates with the closely related αA-crystallin, which has 57% sequence homology with αB-crystallin and shares the conserved ‘α-crystallin domain’ (reviewed in [10]), to form large hetero-oligomeric species. However, it is also constitutively expressed in many non-lenticular tissues, including the brain, lung and cardiac and skeletal muscle where it forms complexes with other sHsps [11].…”

“…The sHsps form a structurally divergent protein family with members present in archaea, bacteria and eukarya [10]. Monomeric molecular masses of the sHsps range between 12 and 40 kDa, however, most form large oligomeric assemblies of 150–800 kDa.…”