13C-NMR off-resonance rotating frame spin-lattice relaxation studies of bovine lens γ-crystallin self association: effect of ‘macromolecular crowding’

Stevens, Arthur; Wang, Sharon X.; Caines, G. Herbert; Schleich, Thomas

doi:10.1016/0167-4838(94)00172-d

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…This gradient is achieved by a variation of protein concentration and crystallin species 53–55 . In human and bovine lenses, α and β crystallins are located mostly in the cortex with lower refractive index and lower protein concentration (200 – 300 mg/ml 56,57 ), and α crystallin was found to be excluded from the lens nucleus 58 . As shown in Figure 1 and Table 1, α and β crystallins also have the lowest dn/dc values in the group of ubiquitous crystallins.…”

Section: Resultsmentioning

confidence: 99%

The Molecular Refractive Function of Lens γ-Crystallins

Zhao

Brown

Magone

et al. 2011

Journal of Molecular Biology

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γ-crystallins constitute the major protein component in the nucleus of the vertebrate eye lens. Present at very high concentrations, they exhibit extreme solubility and thermodynamic stability to prevent scattering of light and the formation of cataracts. However, functions beyond this structural role have remained mostly unclear. Here, we calculate molecular refractive index increments of crystallins. We show that all lens γ-crystallins have evolved a significantly elevated molecular refractive index increment, which is far above those of most proteins, including non-lens members of the βγ-crystallin family from different species. The same trait has evolved in parallel in crystallins of different phyla, including in the S-crystallins of cephalopods. A high refractive index increment can lower the crystallin concentration required to achieve a suitable refractive power of the lens, and thereby reduce their propensity to aggregate and form cataract. To produce a significant increase of the refractive index increment, a substantial global shift in the amino acid composition is required, which can naturally explain the highly unusual amino acid composition of γ-crystallins and their functional homologues. This function provides a new perspective for interpreting their molecular structure.

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Section: Resultsmentioning

confidence: 99%

The Molecular Refractive Function of Lens γ-Crystallins

Zhao

Brown

Magone

et al. 2011

Journal of Molecular Biology

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“…Reduction of configurational space due to steric exclusion and other repulsive intermolecular interactions (e.g., electrostatic) in crowded media can have a significant effect upon the conformation and state of association of each macromolecular species, dilute as well as concentrated, in the medium (10,11). In recent years, it has gradually become recognized that there may exist fundamental differences between protein-protein interactions in crowded and dilute solutions (9,(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Attractive Protein-Polymer Interactions Markedly Alter the Effect of Macromolecular Crowding on Protein Association Equilibria

Jiao

Chen

et al. 2010

Biophysical Journal

131

172

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The dependence of the fluorescence of catalase upon the concentration of added superoxide dismutase (SOD) indicates that SOD binds to saturable sites on catalase. The affinity of SOD for these sites varies with temperature, and with the concentration of each of three nominally inert polymeric additives--dextran 70, Ficoll 70, and polyethylene glycol 2000. At room temperature (25.0 degrees C) and higher, the addition of high concentrations of polymer is found to significantly enhance the affinity of SOD for catalase, but with decreasing temperature the enhancing effect of polymer addition diminishes, and at 8.0 degrees C, addition of polymer has little or no effect on the affinity of SOD for catalase. The results presented here provide the first experimental evidence for the existence of competition between a repulsive excluded volume interaction between protein and polymer, which tends to enhance association of dilute protein, and an attractive interaction between protein and polymer, which tends to inhibit protein association. The net effect of high concentrations of polymer upon protein associations depends upon the relative strength of these two types of interactions at the temperature of measurement, and may vary significantly between different proteins and/or polymers.

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“…They are present at high concentrations so as to generate a high tissue refractive index that allows the lens to focus the light on the retina. Concentrations of 240 mg/ml have been estimated for the cortex of the lens [2], and much higher concentrations of up to 400 – 600 mg/ml and higher [3,4] were estimated for the nucleus of the lens of different animal species. This concentration gradient, in conjunction with a gradient in the distribution of crystallin types [3], supports a spatial refractive index gradient in the lens, which reduces spherical aberration [5].…”

Section: Introductionmentioning

confidence: 99%

“…They are present at high concentrations so as to generate a high tissue refractive index that allows the lens to focus the light on the retina. Concentrations of 240 mg ml −1 have been estimated for the cortex of the lens [2], and much higher concentrations of up to 400-600 mg ml −1 and higher [3,4] were estimated for the nucleus of the lens 1 Author to whom any correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

The role of macromolecular crowding in the evolution of lens crystallins with high molecular refractive index

Zhao

Magone

Schuck³

2011

Phys. Biol.

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Crystallins are present in the lens at extremely high concentrations in order to provide transparency and generate a high refractive power of the lens. The crystallin families prevalent in the highest density lens tissues are γ crystallins in vertebrates and S crystallins in cephalopods. In parallel evolution, both have evolved molecular refractive index increments 5 – 10 % above those of most proteins. Although this is a small increase, it is statistically very significant and can be achieved only by very unusual amino acid compositions. In contrast, such a molecular adaptation to aid in the refractive function of the lens did not occur in crystallins that are preferentially located in lower density lens tissues, such as vertebrate α crystallin and taxon specific crystallins. In the current work, we apply a model of non-interacting hard spheres to examine the thermodynamic contributions of volume exclusion at lenticular protein concentrations. We show that the small concentration decrease afforded by the higher molecular refractive index increment of crystallins can amplify nonlinearly to produce order of magnitude differences in chemical activities, and lead to reduced osmotic pressure and the reduced propensity for protein aggregation. Quantitatively, this amplification sets in only at protein concentrations as high as those found in hard lenses or the nucleus of soft lenses, in good correspondence to the observed crystalline properties in different tissues and different species. This suggests that volume exclusion effects provide the evolutionary driving force for the unusual refractive properties and the unusual amino acid compositions of γ crystallins and S crystallins.

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13C-NMR off-resonance rotating frame spin-lattice relaxation studies of bovine lens γ-crystallin self association: effect of ‘macromolecular crowding’

Cited by 10 publications

References 32 publications

The Molecular Refractive Function of Lens γ-Crystallins

The Molecular Refractive Function of Lens γ-Crystallins

Attractive Protein-Polymer Interactions Markedly Alter the Effect of Macromolecular Crowding on Protein Association Equilibria

The role of macromolecular crowding in the evolution of lens crystallins with high molecular refractive index

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