Dataset Information

Modeling phase transitions in mixtures of ?-? lens crystallins.

ABSTRACT: We analyze the experimentally determined phase diagram of a ?D-?B1 crystallin mixture. Proteins are described as dumbbells decorated with attractive sites to allow inter-particle interaction. We use thermodynamic perturbation theory to calculate the free energy of such mixtures and, by applying equilibrium conditions, also the compositions and concentrations of the co-existing phases. Initially we fit the Tcloudversus packing fraction ? measurements for a pure (x2 = 0) ?D solution in 0.1 M phosphate buffer at pH = 7.0. Another piece of experimental data, used to fix the model parameters, is the isotherm x2vs. ? at T = 268.5 K, at the same pH and salt content. We use the conventional Lorentz-Berthelot mixing rules to describe cross interactions. This enables us to determine: (i) model parameters for pure ?B1 crystallin protein and to calculate; (ii) complete equilibrium surface (Tcloud-x2-?) for the crystallin mixtures. (iii) We present the results for several isotherms, including the tie-lines, as also the temperature-packing fraction curves. Good agreement with the available experimental data is obtained. An interesting result of these calculations is evidence of the coexistence of three phases. This domain appears for the region of temperatures just out of the experimental range studied so far. The input parameters, leading good description of experimental data, revealed a large difference between the numbers of the attractive sites for ?D and ?B1 proteins. This interesting result may be related to the fact that ?D has a more than nine times smaller quadrupole moment than its partner in the mixture.

SUBMITTER: Kastelic M

PROVIDER: S-EPMC5131804 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modeling phase transitions in mixtures of β-γ lens crystallins.

Kastelic Miha M Kalyuzhnyi Yurij V YV Vlachy Vojko V

Soft matter 20160815 35

We analyze the experimentally determined phase diagram of a γD-βB1 crystallin mixture. Proteins are described as dumbbells decorated with attractive sites to allow inter-particle interaction. We use thermodynamic perturbation theory to calculate the free energy of such mixtures and, by applying equilibrium conditions, also the compositions and concentrations of the co-existing phases. Initially we fit the Tcloudversus packing fraction η measurements for a pure (x2 = 0) γD solution in 0.1 M phosp ...[more]

PMID: 27526288

Similar Datasets

Project description:Crystallins are transparent, refractive proteins that contribute to the focusing power of the vertebrate eye lens. These proteins are extremely soluble and resist aggregation for decades, even under crowded conditions. Crystallins have evolved to avoid strong interprotein interactions and have unusual hydration properties. Crystallin aggregation resulting from mutation, damage, or aging can lead to cataract, a disease state characterized by opacity of the lens.Different aggregation mechanisms can occur, following multiple pathways and leading to aggregates with varied morphologies. Studies of variant proteins found in individuals with childhood-onset cataract have provided insight into the molecular factors underlying crystallin stability and solubility. Modulation of exposed hydrophobic surface is critical, as is preventing specific intermolecular interactions that could provide nucleation sites for aggregation. Biophysical measurements and structural biology techniques are beginning to provide a detailed picture of how crystallins crowd into the lens, providing high refractivity while avoiding excessively tight binding that would lead to aggregation.Despite the central biological importance of refractivity, relatively few experimental measurements have been made for lens crystallins. Our work and that of others have shown that hydration is important to the high refractive index of crystallin proteins, as are interactions between pairs of aromatic residues and potentially other specific structural features.This Account describes our efforts to understand both the functional and disease states of vertebrate eye lens crystallins, particularly the ?-crystallins. We use a variety of biophysical techniques, notably NMR spectroscopy, to investigate crystallin stability and solubility. In the first section, we describe efforts to understand the relative stability and aggregation propensity of different ?S-crystallin variants. The second section focuses on interactions of these proteins with the holdase chaperone ?B-crystallin. The third, fourth, and fifth sections explore different modes of aggregation available to crystallin proteins, and the final section highlights the importance of refractive index and the sometimes conflicting demands of selection for refractivity and solubility.

Dataset Information

Modeling phase transitions in mixtures of ?-? lens crystallins.

Publications

Modeling phase transitions in mixtures of β-γ lens crystallins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure