Eye Lens Crystallins: Remarkable
            <scp>Long‐Lived</scp>
            Proteins

Grosas, Aidan B.; Carver, John A.

doi:10.1002/9783527826759.ch3

Cited by 10 publications

(18 citation statements)

References 250 publications

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“…Indeed, such surficial binding of α-crystallin to membranes in clear and young lenses may play a beneficial role in membrane stability. However, age-related changes within membranes (lipid and cholesterol oxidation [ 100 , 101 , 102 , 103 , 104 , 105 ], changes in lipid composition [ 61 , 62 , 68 , 70 , 72 , 73 , 74 , 75 ] and changes in the saturation level of the lipids [ 57 , 63 , 72 , 91 , 92 ]) and in the crystallin proteins (mutations [ 14 , 15 , 16 , 17 ] and post-translational modifications [ 18 , 19 , 20 , 21 , 22 , 106 , 107 , 108 , 109 , 110 , 111 ]) may denature proteins, significantly decrease the chaperone-like activity of α-crystallin and initiate the excessive accumulation of HMWC on the lens membranes. Such excessive accumulation of HMWC blocks the flow of water and small metabolites between the lens membranes and forms a barrier, as described earlier in the old and cataractous lenses [ 37 , 70 , 112 ].…”

Section: Discussionmentioning

confidence: 99%

“…α-Crystallin undergoes various mutations [ 14 , 15 , 16 , 17 ] and post-translational modifications [ 18 , 19 , 20 , 21 , 22 ] with aging, reducing its chaperone-like activity [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Most of the free α-crystallin in the human lens has been used up by the age of 40 years [ 30 , 31 , 32 ], following the significant increase in the level of water-insoluble and higher molecular weight complexes (HMWC) [ 33 , 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

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Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens

Timsina

Wellisch

Haemmerle

et al. 2022

IJMS

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Several studies reported that α-crystallin concentrations in the eye lens cytoplasm decrease with a corresponding increase in membrane-bound α-crystallin with age and cataracts. The influence of the lipid and cholesterol composition difference between cortical membrane (CM) and nuclear membrane (NM) on α-crystallin binding to membranes is still unclear. This study uses the electron paramagnetic resonance (EPR) spin-labeling method to investigate the α-crystallin binding to bovine CM and NM derived from the total lipids extracted from a single lens. Compared to CMs, NMs have a higher percentage of membrane surface occupied by α-crystallin and binding affinity, correlating with less mobility and more order below and on the surface of NMs. α-Crystallin binding to CM and NM decreases mobility with no significant change in order and hydrophobicity below and on the surface of membranes. Our results suggest that α-crystallin mainly binds on the surface of bovine CM and NM and such surface binding of α-crystallin to membranes in clear and young lenses may play a beneficial role in membrane stability. However, with decreased cholesterol content within the CM, which mimics the decreased cholesterol content in the cataractous lens membrane, α-crystallin binding increases the hydrophobicity below the membrane surface, indicating that α-crystallin binding forms a hydrophobic barrier for the passage of polar molecules, supporting the barrier hypothesis in developing cataracts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens

Timsina

Wellisch

Haemmerle

et al. 2022

IJMS

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“…The studies using in-vitro assays and site-directed mutagenesis have suggested that α-crystallin usually is stable and can tolerate the substitution of its many amino acids in its primary structure [205,206]. Several mutations leading to cataract formation have been reported [207][208][209][210]. A missense mutation of the arginine 116 residue to cysteine (R116C) in αA-crystallin decreases the chaperone-like activity of α-crystallin approximately four-fold, reduces the ability to exchange α-crystallin's subunits four-fold, and increases the membrane-binding capacity 10-fold [208].…”

Section: Interaction Of α-Crystallin With the Lens Integral Membrane Proteinsmentioning

confidence: 99%

“…Grosas and Carver et al [210] discussed several other α-crystallin mutations leading to cataract formation. We speculate that future investigations will discover additional mutations leading to cataract formation and progression.…”

Section: Mutations Andmentioning

confidence: 99%

“…α-crystallin binds to other lens proteins forming higher molecular weight complexes (HMWCs), and the association of HMWCs with lens membrane increases with age and cataract [76][77][78]. Moreover, various α-crystallin mutations and PTMs correlate with cataracts [210], implying that these mutations and PTMs likely change the structure of α-crystallin, leading to large-scale crystallin precipitation, followed by association with the lens membranes and cataract formation.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Association of Alpha-Crystallin with Fiber Cell Plasma Membrane of the Eye Lens Accompanied by Light Scattering and Cataract Formation

Timsina

Mainali

2021

Membranes

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α-crystallin is a major protein found in the mammalian eye lens that works as a molecular chaperone by preventing the aggregation of proteins and providing tolerance to stress in the eye lens. These functions of α-crystallin are significant for maintaining lens transparency. However, with age and cataract formation, the concentration of α-crystallin in the eye lens cytoplasm decreases with a corresponding increase in the membrane-bound α-crystallin, accompanied by increased light scattering. The purpose of this review is to summarize previous and recent findings of the role of the: 1) lens membrane components, i.e., the major phospholipids (PLs) and sphingolipids, cholesterol (Chol), cholesterol bilayer domains (CBDs), and the integral membrane proteins aquaporin-0 (AQP0; formally MIP26) and connexins, and 2) α-crystallin mutations and post-translational modifications (PTMs) in the association of α-crystallin to the eye lens’s fiber cell plasma membrane, providing thorough insights into a molecular basis of such an association. Furthermore, this review highlights the current knowledge and need for further studies to understand the fundamental molecular processes involved in the association of α-crystallin to the lens membrane, potentially leading to new avenues for preventing cataract formation and progression.

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Using Capillary Electrophoresis to Investigate Protein Conformational and Compositional Heterogeneity

Grosas,

Du Plessis,

Thevarajah

et al. 2024

ChemBioChem

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Detailed insights into protein structure/function relationships require robust characterization methodologies. Free‐solution capillary electrophoresis (CE) is a unique separation technique which is sensitive to the conformation and/or composition of proteins, and therefore provides information on the heterogeneity of these properties. Three unrelated, conformationally/compositionally‐altered proteins were separated by CE. An electrophoretic mobility distribution was determined for each protein along with its conformational and/or compositional heterogeneity. CE results were compared with molar mass distributions obtained from size‐exclusion chromatography coupled to light scattering (SEC‐MALS). Bovine serum albumin oligomers and two monomeric species were separated, highlighting variations in conformational/compositional heterogeneity among the oligomers. Analysis of yeast alcohol dehydrogenase resolved two monomeric conformers and various tetrameric species, illustrating the impact of zinc ion removal and disulfide bond reduction on the protein’s heterogeneity. The apo (calcium‐free) and holo forms of bovine α‐lactalbumin were separated and differences in the species’ heterogeneity was measured; by contrast, the SEC‐MALS profiles were identical. Comparative analysis of these structurally unrelated proteins provided novel insights into the interplay between molar mass and conformational/compositional heterogeneity. Overall, this study expands the utility of CE by demonstrating its capacity to discern protein species and their heterogeneity, properties which are not readily accessible by other analytical techniques.

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Eye Lens Crystallins: Remarkable Long‐Lived Proteins

Cited by 10 publications

References 250 publications

Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens

Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens

Association of Alpha-Crystallin with Fiber Cell Plasma Membrane of the Eye Lens Accompanied by Light Scattering and Cataract Formation

Using Capillary Electrophoresis to Investigate Protein Conformational and Compositional Heterogeneity

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