An alternative splice variant of human αA-crystallin modulates the oligomer ensemble and the chaperone activity of α-crystallins.
In humans, ten genes encode small heat shock proteins with lens αA-crystallin and αB-crystallin representing two of the most prominent members. The canonical isoforms of αA-crystallin and αB-crystallin collaborate in the eye lens to prevent irreversible protein aggregation and preserve visual acuity. α-Crystallins form large polydisperse homo-oligomers and hetero-oligomers and as part of the proteostasis system bind substrate proteins in non-native conformations, thereby stabilizing them. Here, we analyzed a previously uncharacterized, alternative splice variant (isoform 2) of human αA-crystallin with an exchanged N-terminal sequence. This variant shows the characteristic α-crystallin secondary structure, exists on its own predominantly in a monomer-dimer equilibrium, and displays only low chaperone activity. However, the variant is able to integrate into higher order oligomers of canonical αA-crystallin and αB-crystallin as well as their hetero-oligomer. The presence of the variant leads to the formation of new types of higher order hetero-oligomers with an overall decreased number of subunits and enhanced chaperone activity. Thus, alternative mRNA splicing of human αA-crystallin leads to an additional, formerly not characterized αA-crystallin species which is able to modulate the properties of the canonical ensemble of α-crystallin oligomers.
['Preis|Waldemar|W|', 'Bestehorn|Annika|A|', 'Buchner|Johannes|J|', 'Haslbeck|Martin|M|']
D017398:Alternative Splicing D006801:Humans D011485:Protein Binding D011487:Protein Conformation D017510:Protein Folding D020033:Protein Isoforms D055503:Protein Multimerization D012333:RNA, Messenger D038202:alpha-Crystallin A Chain D038203:alpha-Crystallin B Chain
Alternative splicing Alpha-crystallin Chaperone function Protein folding sHsp