Alpha B- and βA3-crystallins containing d-Aspartic acids exist in a monomeric state

Sakaue, Hiroaki; Takata, Takumi; Fujii, Norihiko; Sekiya, Hiroshi; Fujii, Nobutaka

doi:10.1016/j.bbapap.2014.10.006

Cited by 29 publications

(27 citation statements)

References 25 publications

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“…That finding indicated that inversion of Asp residues may induce dissociation of αB‐crystallin from the polymeric state. Although d ‐Asp‐containing monomeric αB‐crystallin was found, the possibility of the presence of αA‐crystallin was not observed . In this study, monomeric αA‐crystallin with high levels of Asp isomerization was identified; thus, dissociation of α‐crystallin heteropolymers was confirmed in vivo .…”

Section: Discussionmentioning

confidence: 60%

“…In the past studies, we have reported that isomerization of Asp increased in the water‐insoluble fractions in the lens crystallins from elderly donors . In addition to those results, we recently found that native polymeric αB‐crystallin dissociated to the monomeric state, and Asp96 of monomeric αB‐crystallin was highly inverted, which does not occur in native polymeric αB‐crystallin . That finding indicated that inversion of Asp residues may induce dissociation of αB‐crystallin from the polymeric state.…”

Section: Discussionmentioning

confidence: 68%

“…Recently, we observed increasing Asp isomerization at Asp96 of the αB‐crystallin monomeric fraction in aged lens . Isomerization of Asp96 was not increased in the higher order heteropolymeric fraction of lens crystallins, implying that isomerization of Asp might induce dissociation of the αB‐crystallin subunit from α‐crystallin heteropolymers in aged lens.…”

Section: Introductionmentioning

confidence: 84%

“…This is because it has been believed that α‐ and β‐crystallins retain multimeric states in vivo . However, we recently detected that multimeric α‐ and β‐crystallins dissociated to monomeric proteins in the lenses of age‐related cataracts . Here, therefore, we focused on the size‐dependent differences in the PTMs of α‐crystallin, by examining the heteropolymer and monomeric fractions in aged lens.…”

Section: Introductionmentioning

confidence: 99%

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Isomerization of Asp residues plays an important role in αA‐crystallin dissociation

Takata

Fujii

2016

The FEBS Journal

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Aged cataract formation is caused by the accumulative precipitation of lens proteins incorporating diverse post-translational modifications. a-Crystallin, a major structural and functional lens protein, consists of a large polymeric structure that is dissociated and insolubilized with accumulative post-translational modifications. One such modification, isomerization of Asp, was recently identified in aB-crystallin monomers derived from aged lens. However, the distributions of Asp isomers in each lens fraction remain unknown. Here, a-crystallin fractions from aged lens were separated into heteropolymeric and monomeric forms to determine the Asp isomerization ratios in each fraction. Lens of four different ages were homogenized and centrifuged, and the soluble fraction was applied to size-exclusion chromatography. The heteropolymeric a-crystallin and monomeric crystallin fractions were obtained and concentrated. After trypsin digestion, each fraction was independently applied to liquid chromatography equipped with mass spectrometry to extract a-crystallin-derived peptides containing Asp isomers. The results showed that Asp58, Asp84 and Asp151 of aA-crystallin were highly isomerized in the monomeric fraction, but not isomerized to the same level in the heteropolymeric fraction. Each type of Asp isomerization increased in an age-dependent manner, was site-specific and was similar to previous results from lens water-insoluble fractions. These results imply that isomerization of Asp residues leads to dissociation of aA-crystallin from the heteropolymeric state and induces insolubilization in aged lens. Taken together, our findings suggest that isomerization of Asp might disrupt the higher order polymeric state of a-crystallin, resulting in decreased solubility and function, ultimately contributing to lens protein impairment and cataract formation with aging.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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Isomerization of Asp residues plays an important role in αA‐crystallin dissociation

Takata

Fujii

2016

The FEBS Journal

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“…On the other hand, we recently reported that the inversion of Asp residues induced the dissociation of αB-and βA3-crystallin of elderly donor lens from a polymeric and oligomeric state [42], which shows that stereoinversion of Asp residues disturbs lens protein assembly in aged human lens. Damino acid substitutions might actively alter the structural formation and function of protein or peptides.…”

Section: Effects On the Property And Function Of Crystallin By Isomermentioning

confidence: 98%

Isomerization of aspartyl residues in crystallins and its influence upon cataract

Fujii

Takata

Fujii

et al. 2016

Biochimica et Biophysica Acta (BBA) - General Subjects

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Modifications of Long‐Lived Proteins that Affect Protein Solubility

David

2021

Long‐lived Proteins in Human Aging and Disease

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Alpha B- and βA3-crystallins containing d-Aspartic acids exist in a monomeric state

Cited by 29 publications

References 25 publications

Isomerization of Asp residues plays an important role in αA‐crystallin dissociation

Isomerization of Asp residues plays an important role in αA‐crystallin dissociation

Isomerization of aspartyl residues in crystallins and its influence upon cataract

Modifications of Long‐Lived Proteins that Affect Protein Solubility

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