Structural highlights
Disease[CRYGS_HUMAN] Early-onset lamellar cataract;Early-onset sutural cataract. The disease is caused by mutations affecting the gene represented in this entry. Function[CRYGS_HUMAN] Crystallins are the dominant structural components of the vertebrate eye lens. Publication Abstract from PubMedA recently identified mutant of human gammaS-crystallin, G57W is associated with dominant congenital cataracts, the familial determinate of childhood blindness worldwide. To investigate the structural and functional changes that mediate the effect of this cataract-related mutant to compromise eye lens transparency and cause lens opacification in children, we recently reported complete sequence-specific resonance assignments of gammaS-G57W using a suite of heteronuclear NMR experiments. As a follow up, we have determined the 3D structure of gammaS-G57W and studied its conformational dynamics by solution NMR spectroscopy. Our structural dynamics results reveal greater flexibility of the N-terminal domain, which undergoes site-specific structural changes to accommodate W57, than its C-terminal counterpart. Our structural inferences that the unusual solvent exposure of W57 is associated with rearrangement of the N-terminal domain suggest an efficient pathway for increased aggregation in gammaS-G57W and illuminates the molecular dynamics underlying cataractogenic aggregation of lens crystallins in particular and aggregation of proteins in general. Structure of G57W mutant of human gammaS-crystallin and its involvement in cataract formation.,Bari KJ, Sharma S, Chary KVR J Struct Biol. 2019 Mar 1;205(3):72-78. doi: 10.1016/j.jsb.2019.02.003. Epub 2019, Feb 12. PMID:30769148[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 07:22, 10 April 2019.