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Stability and aggregation differences in two lens γ‐crystallins, proteins implicated in cataract
Author(s) -
Mills Ishara A,
Flaugh Shan L.,
King Jonathan A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb29-b
Subject(s) - crystallin , chemistry , lens (geology) , biophysics , biochemistry , biology , paleontology
The transparency of the eye lens depends on the high solubility and stability of the crystallin proteins. Aggregation of partially unfolded or covalently damaged forms results in mature‐onset cataracts. Thus, the biochemical basis of the extremely high stability of the crystallins, and the nature of the misfolded, modified, or aggregated states, are important in understanding the etiology of cataract. We analyzed the biophysical properties of human γD crystallin (γD‐Crys) and human γS crystallin (γS‐Crys), two of the most abundant proteins in the lens. γD‐Crys is synthesized in utero and must remain soluble throughout life in the differentiated enucleated lens fiber cells. In contrast, γS‐Crys is expressed postpartum and throughout life in the fiber cells. Comparison of these proteins’s conformational stability indicated that γD‐Crys is more stable than γS‐Crys. In addition, we analyzed the unfolding kinetic rates of γD‐Crys and γS‐Crys. γD‐Crys was highly stable kinetically with an extrapolated half‐life of 19 years while γS‐Crys had a 7.5 hour half‐life for the first kinetic unfolding step. Although structurally similar, these crystallins exhibit different conformational and kinetic stability with γD‐Crys more stable than γS‐Crys. Given the physiological differences of these crystallins in the lens, these results demonstrate the high stability requirement for long‐lived crystallins in the lens.