Identification of Sequence Similarities among Isomerization Hotspots in Crystallin Proteins

The eye lens crystallins represent an ideal target for studying the effects of aging on protein structure. Herein we examine separately the water-soluble (WS) and water-insoluble (WI) crystallin fractions and identify sites of isomerization and epimerization. Both collision-induced dissociation and...

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Bibliographic Details
Published in:Journal of proteome research 2017-04, Vol.16 (4), p.1797-1805
Main Authors: Lyon, Yana A, Sabbah, Georgette M, Julian, Ryan R
Format: Article
Language:English
Subjects:
Aging - genetics
Aging - metabolism
Aging - pathology
Amino Acid Sequence - genetics
Animals
Cataract - genetics
Cataract - metabolism
Cataract - pathology
Cattle
Crystallins - chemistry
Crystallins - isolation & purification
Crystallins - metabolism
Humans
Lens, Crystalline - metabolism
Protein Conformation
Protein Processing, Post-Translational - genetics
Sheep
Solubility
Swine
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Summary:The eye lens crystallins represent an ideal target for studying the effects of aging on protein structure. Herein we examine separately the water-soluble (WS) and water-insoluble (WI) crystallin fractions and identify sites of isomerization and epimerization. Both collision-induced dissociation and radical-directed dissociation are needed for detection of these non-mass-shifting post-translational modifications. Isomerization levels differ significantly between the WS and the WI fractions from sheep, pig, and cow eye lenses. Residues that are most susceptible to isomerization are identified site-specifically and are found to reside in structurally disordered regions. However, isomerization in structured domains, although less common, often yields more dramatic effects on solubility. Numerous isomerization hotspots were also identified and occur in regions with aspartic acid and serine repeats. For example, 128KME­IVD­DDV­PSLW140 in βB3 crystallin contains three sequential aspartic acid residues and is isomerized heavily in the WI fractions, while it is not modified at all in the WS fractions. Potential causes for enhanced isomerization at sites with acidic residue repeats are presented. The importance of acidic residue repeats extends beyond the lens, as they are found in many other long-lived proteins associated with disease.
ISSN:1535-3893
1535-3907
DOI:10.1021/acs.jproteome.7b00073