2M3U

Solution-state NMR structure of cataract-related human gamma(S)-crystallin point variant G18V

Summary for 2M3U

• Entry DOI: 10.2210/pdb2m3u/pdb
• Related: 2M3T
• NMR Information: BMRB: 17582
• Descriptor: Beta-crystallin S (1 entity in total)
• Functional Keywords: gamma-s, eye lens, aggregation, crystallin, cataract, crygs, structural protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 21001.71

Authors

Brubaker, W.D.,Martin, R.W. (deposition date: 2013-01-25, release date: 2013-11-13, Last modification date: 2024-05-01)

Primary citation

Kingsley, C.N.,Brubaker, W.D.,Markovic, S.,Diehl, A.,Brindley, A.J.,Oschkinat, H.,Martin, R.W.
Preferential and Specific Binding of Human alpha B-Crystallin to a Cataract-Related Variant of gamma S-Crystallin.
Structure, 21:2221-2227, 2013

PubMed Abstract: Transparency in the eye lens is maintained via specific, functional interactions among the structural βγ- and chaperone α-crystallins. Here, we report the structure and α-crystallin binding interface of the G18V variant of human γS-crystallin (γS-G18V), which is linked to hereditary childhood-onset cortical cataract. Comparison of the solution nuclear magnetic resonance structures of wild-type and G18V γS-crystallin, both presented here, reveal that the increased aggregation propensity of γS-G18V results from neither global misfolding nor the solvent exposure of a hydrophobic residue but instead involves backbone rearrangement within the N-terminal domain. αB-crystallin binds more strongly to the variant, via a well-defined interaction surface observed via chemical shift differences. In the context of the αB-crystallin structure and the finding that it forms heterogeneous multimers, our structural studies suggest a potential mechanism for cataract formation via the depletion of the finite αB-crystallin population of the lens.

PubMed: 24183572
DOI: 10.1016/j.str.2013.09.017

Experimental method

SOLUTION NMR