Interaction of α-crystallin with some small molecules and its effect on its structure and function

• Published in: Biochimica et biophysica acta Vol. 1860; no. 1; pp. 211 - 221
• Main Authors: Biswas, A., Karmakar, S., Chowdhury, A., Das, K.P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2016
• Subjects: adenosine triphosphate; Adenosine Triphosphate - chemistry; alpha-Crystallins - chemistry; alpha-Crystallins - ultrastructure; ATP binding; Binding Sites; cataract; Chaperone function of alpha crystallin; dissociation; enzyme activity; fluorescence; Hydrophobic and Hydrophilic Interactions; Hydrophobic probe; hydrophobicity; Lens peptide; metal ions; Metals - chemistry; Models, Chemical; molecular chaperones; peptides; Peptides - chemistry; Protein Binding; Protein Conformation; Small molecule interaction; Structure-Activity Relationship; Surface-Active Agents - chemistry; surfactants; Chaperone function of alpha crystallin; Hydrophobic probe; Lens peptide; ATP binding; Small molecule interaction
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2015.06.002

α-Crystallin acts like a molecular chaperone by interacting with its substrate proteins and thus prevents their aggregation. It also interacts with various kinds of small molecules that affect its structure and function. In this article we will present a review of work done with respect to the interaction of ATP, peptide generated from lens crystallin and other proteins and some bivalent metal ions with α-crystallin and discuss the role of these interactions on its structure and function and cataract formation. We will also discuss the interaction of some hydrophobic fluorescence probes and surface active agents with α-crystallin. Small molecule interaction controls the structure and function of α-crystallin. ATP and Zn+2 stabilize its structure and enhance chaperone function. Therefore the depletion of these small molecules can be detrimental to maintenance of lens transparency. However, the accumulation of small peptides due to protease activity in the lens can also be harmful as the interaction of these peptides with α-crystallin and other crystallin proteins in the lens promotes aggregation and loss of lens transparency. The use of hydrophobic probe has led to a wealth of information regarding the location of substrate binding site and nature of chaperone–substrate interaction. Interaction of surface active agents with α-crystallin has helped us to understand the structural stability and oligomeric dissociation in α-crystallin. These interactions are very helpful in understanding the mechanistic details of the structural changes and chaperone function of α-crystallin. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. •Many small molecules bind with α-crystallin affecting its structure and function.•ATP and Zn+2 stabilize α-crystallin structure and enhance its chaperone function.•Accumulation of lens peptides can promote cataract formation.•Hydrophobic probe binding helped in identifying chaperone site of α-crystallin.•Some surfactants can affect oligomer dissociation and structural dynamics.