The structure and oxidation of the eye lens chaperone αA-crystallin.

Nature structural & molecular biology 2019 Dec

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The small heat shock protein αA-crystallin is a molecular chaperone important for the optical properties of the vertebrate eye lens. It forms heterogeneous oligomeric ensembles. We determined the structures of human αA-crystallin oligomers by combining cryo-electron microscopy, cross-linking/mass spectrometry, NMR spectroscopy and molecular modeling. The different oligomers can be interconverted by the addition or subtraction of tetramers, leading to mainly 12-, 16- and 20-meric assemblies in which interactions between N-terminal regions are important. Cross-dimer domain-swapping of the C-terminal region is a determinant of αA-crystallin heterogeneity. Human αA-crystallin contains two cysteines, which can form an intramolecular disulfide in vivo. Oxidation in vitro requires conformational changes and oligomer dissociation. The oxidized oligomers, which are larger than reduced αA-crystallin and destabilized against unfolding, are active chaperones and can transfer the disulfide to destabilized substrate proteins. The insight into the structure and function of αA-crystallin provides a basis for understanding its role in the eye lens.

Citation

Christoph J O Kaiser, Carsten Peters, Philipp W N Schmid, Maria Stavropoulou, Juan Zou, Vinay Dahiya, Evgeny V Mymrikov, Beate Rockel, Sam Asami, Martin Haslbeck, Juri Rappsilber, Bernd Reif, Martin Zacharias, Johannes Buchner, Sevil Weinkauf. The structure and oxidation of the eye lens chaperone αA-crystallin. Nature structural & molecular biology. 2019 Dec;26(12):1141-1150