期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 26, 期 12, 页码 1141-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41594-019-0332-9
关键词
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资金
- Deutsche Forschungsgemeinschaft [SFB 1035]
- CIPSM
- Wellcome Trust [103139, 203149]
The small heat shock protein alpha A-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 alpha A-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 alpha A-crystallin heterogeneity. Human alpha A-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 alpha A-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 alpha A-crystallin provides a basis for understanding its role in the eye lens.
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