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Publication Abstract from PubMed

The small heat shock protein alphaA-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 alphaA-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 alphaA-crystallin heterogeneity. Human alphaA-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 alphaA-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 alphaA-crystallin provides a basis for understanding its role in the eye lens.

The structure and oxidation of the eye lens chaperone alphaA-crystallin.,Kaiser CJO, Peters C, Schmid PWN, Stavropoulou M, Zou J, Dahiya V, Mymrikov EV, Rockel B, Asami S, Haslbeck M, Rappsilber J, Reif B, Zacharias M, Buchner J, Weinkauf S Nat Struct Mol Biol. 2019 Dec;26(12):1141-1150. doi: 10.1038/s41594-019-0332-9., Epub 2019 Dec 2. PMID:31792453^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.