| 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 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.
References
- ↑ Thampi P, Hassan A, Smith JB, Abraham EC. Enhanced C-terminal truncation of alphaA- and alphaB-crystallins in diabetic lenses. Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3265-72. PMID:12356833
- ↑ Nagaraj RH, Nahomi RB, Shanthakumar S, Linetsky M, Padmanabha S, Pasupuleti N, Wang B, Santhoshkumar P, Panda AK, Biswas A. Acetylation of alphaA-crystallin in the human lens: effects on structure and chaperone function. Biochim Biophys Acta. 2012 Feb;1822(2):120-9. doi: 10.1016/j.bbadis.2011.11.011. , Epub 2011 Nov 18. PMID:22120592 doi:http://dx.doi.org/10.1016/j.bbadis.2011.11.011
- ↑ 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. The structure and oxidation of the eye lens chaperone alphaA-crystallin. Nat Struct Mol Biol. 2019 Dec;26(12):1141-1150. doi: 10.1038/s41594-019-0332-9., Epub 2019 Dec 2. PMID:31792453 doi:http://dx.doi.org/10.1038/s41594-019-0332-9
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