4GR7

The human W42R Gamma D-Crystallin Mutant Structure at 1.7A Resolution

4GR7 の概要

• エントリーDOI: 10.2210/pdb4gr7/pdb
• 分子名称: Gamma-crystallin D, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: cataract, greek key motif, structural protein, lens fiber cell
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41306.87

構造登録者

Ji, F.,Jung, J.,Koharudin, L.M.I.,Gronenborn, A.M. (登録日: 2012-08-24, 公開日: 2012-11-07, 最終更新日: 2023-09-13)

主引用文献

Ji, F.,Jung, J.,Koharudin, L.M.,Gronenborn, A.M.
The human W42R gamma D-crystallin mutant structure provides a link between congenital and age-related cataracts.
J.Biol.Chem., 288:99-109, 2013

PubMed Abstract: Some mutants of human γD-crystallin are closely linked to congenital cataracts, although the detailed molecular mechanisms of mutant-associated cataract formation are generally not known. Here we report on a recently discovered γD-crystallin mutant (W42R) that has been linked to autosomal dominant, congenital cataracts in a Chinese family. The mutant protein is much less soluble and stable than wild-type γD-crystallin. We solved the crystal structure of W42R at 1.7 Å resolution, which revealed only minor differences from the wild-type structure. Interestingly, the W42R variant is highly susceptible to protease digestion, suggesting the presence of a small population of partially unfolded protein. This partially unfolded species was confirmed and quantified by NMR spectroscopy. Hydrogen/deuterium exchange experiments revealed chemical exchange between the folded and unfolded species. Exposure of wild-type γD-crystallin to UV caused damage to the N-terminal domain of the protein, resulting in very similar proteolytic susceptibility as observed for the W42R mutant. Altogether, our combined data allowed us to propose a model for W42R pathogenesis, with the W42R mutant serving as a mimic for photodamaged γD-crystallin involved in age-related cataract.

PubMed: 23124202
DOI: 10.1074/jbc.M112.416354

実験手法

X-RAY DIFFRACTION (1.7 Å)