6IF9

Solution-state NMR structure of G57W human gammaS crystallin

Summary for 6IF9

• Entry DOI: 10.2210/pdb6if9/pdb
• Descriptor: Gamma-crystallin S (1 entity in total)
• Functional Keywords: structure from cyana 3.97, recombination
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 21162.94

Authors

Sharma, S.,Bari, K.J.,Chary, K.V.R. (deposition date: 2018-09-19, release date: 2019-04-10, Last modification date: 2024-05-15)

Primary citation

Bari, K.J.,Sharma, S.,Chary, K.V.R.
Structure of G57W mutant of human gamma S-crystallin and its involvement in cataract formation.
J. Struct. Biol., 205:72-78, 2019

PubMed Abstract: A recently identified mutant of human γS-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 γS-G57W using a suite of heteronuclear NMR experiments. As a follow up, we have determined the 3D structure of γS-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 γS-G57W and illuminates the molecular dynamics underlying cataractogenic aggregation of lens crystallins in particular and aggregation of proteins in general.

PubMed: 30769148
DOI: 10.1016/j.jsb.2019.02.003

Experimental method

SOLUTION NMR