6t1r
From Proteopedia
Pseudo-atomic model of a 16-mer assembly of reduced recombinant human alphaA-crystallin (non domain swapped configuration)
Structural highlights
Disease[CRYAA_HUMAN] Early-onset lamellar cataract;Early-onset nuclear cataract;Total early-onset cataract;Cataract-microcornea syndrome;Early-onset anterior polar cataract. Alpha-crystallin A 1-172 is found at nearly twofold higher levels in diabetic lenses than in age-matched control lenses.[1] The disease is caused by mutations affecting the gene represented in this entry. Function[CRYAA_HUMAN] Contributes to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions.[2] Publication Abstract from PubMedThe 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. References
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