Dataset Information

Ion-activated attractive patches as a mechanism for controlled protein interactions.

ABSTRACT: The understanding of protein interactions to control phase and nucleation behavior of protein solutions is an important challenge for soft matter, biological and medical research. Here, we present ion bridges of multivalent cations between proteins as an ion-activated mechanism for patchy interaction that is directly supported by experimental findings in protein crystals. A deep understanding of experimentally observed phenomena in protein solutions--including charge reversal, reentrant condensation, metastable liquid-liquid phase separation, cluster formation and different pathways of crystallization--is gained by an analytic model that directly displays parameter dependencies and physical connections. The direct connection between experiment and theory provides a conceptual framework for future experimental, computational and theoretical research on topics such as rational design of phase behavior and crystallization pathways on the basis of the statistical physics of patchy particles.

SUBMITTER: Roosen-Runge F

PROVIDER: S-EPMC5382698 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ion-activated attractive patches as a mechanism for controlled protein interactions.

Roosen-Runge Felix F Zhang Fajun F Schreiber Frank F Roth Roland R

Scientific reports 20141112

The understanding of protein interactions to control phase and nucleation behavior of protein solutions is an important challenge for soft matter, biological and medical research. Here, we present ion bridges of multivalent cations between proteins as an ion-activated mechanism for patchy interaction that is directly supported by experimental findings in protein crystals. A deep understanding of experimentally observed phenomena in protein solutions--including charge reversal, reentrant condensa ...[more]

PMID: 25388788

Similar Datasets

Project description:Deamidation of proteins is one of the most prevalent post-translational modifications found upon aging, and in age-onset diseases. Specific asparagine and glutamine residues are often selectively deamidated during this process. In the human lens, deamidation has been shown to occur in many crystallins, but it is not clear how these deamidated proteins lead to lens opacity or cataract. Here we have modeled in vitro the effect of deamidation of specific asparagine and glutamine residues in human recombinant ?S-crystallin (HGS) on the solution properties of the protein. The residues selected for deamidation in vitro are those that are found to be deamidated in aged and cataractous lenses in vivo. Two derivatives were prepared, one with Asn76 and Asn143 deamidated (2N-HGS) and the other with two additional Gln residues (92 and 120) deamidated (2N2Q-HGS). Isoelectric focusing measurements showed the expected lowering of the pI from 6.9 in HGS to ?6.5 in 2N-HGS and to ?6.1 in 2N2Q-HGS. However, spectroscopic studies showed no significant change in the secondary and tertiary structures of the deamidated proteins relative to the wild type. The stability of 2N-HGS and 2N2Q-HGS, as measured by guanidinium hydrochloride unfolding, also remained comparable to that of HGS. The main difference was the altered protein-protein interaction among the three proteins. The net repulsive interactions that are characteristic of HGS are diminished in the deamidated derivatives as evidenced by static light scattering measurements of the second virial coefficient, B2 (B2 values for HGS, 2N-HGS, and 2N2Q-HGS of 8.90 × 10(-4), 7.10 × 10(-4), and 6.65 × 10(-4) mL mol g(-2), respectively). Further substantiation is provided by estimates of the excess binding energy of protein-protein interactions in the condensed phase, obtained from measurements of the PEG-induced liquid-liquid phase separation profiles for the three proteins. The data suggest that enhanced attractive protein-protein interactions, arising from the deamidation of HGS, promote protein aggregation, thereby leading to increased light scattering and opacity over time.

Dataset Information

Ion-activated attractive patches as a mechanism for controlled protein interactions.

Publications

Ion-activated attractive patches as a mechanism for controlled protein interactions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets