Structure and function of α-crystallins: Traversing from in vitro to in vivo

• Published in: Biochimica et biophysica acta Vol. 1860; no. 1; pp. 149 - 166
• Main Authors: Haslbeck, Martin, Peschek, Jirka, Buchner, Johannes, Weinkauf, Sevil
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2016
• Subjects: alpha-Crystallins - chemistry; alpha-Crystallins - metabolism; alpha-Crystallins - ultrastructure; Amino Acid Sequence; Animals; Binding Sites; cataract; Cataract - metabolism; Cataract - pathology; Crystallin; crystallins; Eye lens; heat shock proteins; Humans; In Vitro Techniques; Lens, Crystalline - chemistry; Lens, Crystalline - metabolism; Lens, Crystalline - ultrastructure; light scattering; longevity; methodology; Molecular chaperone; Molecular Sequence Data; Protein Binding; Protein Conformation; Protein dynamics; protein metabolism; Small heat shock protein; Structure-Activity Relationship; αA; αB; Crystallin; sHsp; Small heat shock protein; αL; Protein dynamics; GAPDH; Molecular chaperone; Eye lens
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2015.06.008

The two α-crystallins (αA- and αB-crystallin) are major components of our eye lenses. Their key function there is to preserve lens transparency which is a challenging task as the protein turnover in the lens is low necessitating the stability and longevity of the constituent proteins. α-Crystallins are members of the small heat shock protein family. αB-crystallin is also expressed in other cell types. The review summarizes the current concepts on the polydisperse structure of the α-crystallin oligomer and its chaperone function with a focus on the inherent complexity and highlighting gaps between in vitro and in vivo studies. Both α-crystallins protect proteins from irreversible aggregation in a promiscuous manner. In maintaining eye lens transparency, they reduce the formation of light scattering particles and balance the interactions between lens crystallins. Important for these functions is their structural dynamics and heterogeneity as well as the regulation of these processes which we are beginning to understand. However, currently, it still remains elusive to which extent the in vitro observed properties of α-crystallins reflect the highly crowded situation in the lens. Since α-crystallins play an important role in preventing cataract in the eye lens and in the development of diverse diseases, understanding their mechanism and substrate spectra is of importance. To bridge the gap between the concepts established in vitro and the in vivo function of α-crystallins, the joining of forces between different scientific disciplines and the combination of diverse techniques in hybrid approaches are necessary. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. •α-Crystallins (αA-, αB-crystallin and their mixture α-crystallin) maintain lens transparency.•As small heat shock proteins, α-crystallins protect unfolding proteins from aggregation.•α-Crystallins form dynamic, polydisperse homo- and hetero-oligomers of different properties.•The structural dynamics and heterogeneity of α-crystallins are key for their chaperone function.•The complexity of α-crystallins and current gaps between in vitro and in vivo studies are highlighted.