Can charge-reversal be considered as a strategy for attaining thermal stability in proteins?

Do charge reversal mutations (CRM) naturally occur in mesophilic-thermophilic/hyperthermophilic (M-T/HT) orthologous proteins? Do they contribute to thermal stability by altering charge-charge interactions? A careful investigation on 1550 M-T/HT orthologous protein pairs with remarkable structural and topological similarity extracts the role of buried and partially exposed CRMs in enhancing thermal stability. Our findings could assist in engineering thermo-stable variants of proteins.

A Zeta Potentiometric Study on Effects of Ionic Composition and Rock-Saturation on Surface-Charge Interactions in Low-Salinity Water Flooding for Carbonate Formation

As carbonate reservoirs are mostly oil-wet, the potential for the success of a waterflooding is lower. Therefore, a primary focus during waterflooding such reservoirs is on the ionic composition and salinity of injected brine which are able to impact the alteration of the rock wettability favorably by altering the surface charge towards a higher negative value or close to zero. The objective of this study is to employ zeta potentiometric studies comprising streaming potential and streaming current techniques to quantify the surface interactions and charges between the carbonate rock and fluid type as a function of the variations in its ionic state and rock saturation. Zeta potentiometric studies were conducted on carbonate rock samples to understand the behavior of different aqueous solutions by variation in the brine's salinity and ionic composition and the results were integrated with wettability studies. The concentrations of potential-determining ions (PDIs) such as SO42-, Mg2+ and Ca2+ in the injected brines are deemed responsible for altering the wettability state of the carbonate rocks. Several diluted brines (25%, 10% and 1% diluted seawater) and smart brines have been investigated. Smart brines were prepared by spiking the concentration of major PDIs. All zeta potential measurements were conducted using a specially designed zeta potentiometer sample-holding clamp capable of using the whole core plugs rather than pulverized rock samples. A major advantage of using the whole core sample is that the same core can be used in subsequent coreflooding tests, thus making zeta potentiometric results more relevant and representative for a particular rock-fluid system used in the study. The classical streaming potential and streaming current techniques were used for zeta potential measurement. The Fairbrother-Mastin approach was used where the streaming potential is measured against different pressure differentials. Measurements were also carried out for brines with rock samples of different states: oil-saturated, water-saturated and rock samples cleaned with organic solvents to determine any likely variations in surface charge interactions. The results of our experiments imply that the value of zeta potential either increases or becomes more negative with increasing percentage of dilution (25%, 10%, and 1%). This can be attributed to electrical double-layer expansion which is primarily caused by reduced ionic strength. Furthermore, with measurements done on smart brines, zeta potential value was also found to be increased when different diluted brines are spiked with ionic concentration of PDIs such as sulfate. This could have been caused by surface ion alteration mechanism where PDIs get adsorbed on rock surface causing possible detachment of oil droplets. Both the phenomena are known mechanisms for altering wettability towards more water wetness in carbonate rocks and are discussed in detail.

The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation

While aggregation-prone proteins are known to accelerate ageing and cause age-related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG-4, SERF1A and SERF2 have recently been identified as cellular modifiers of such cytotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with specific patterns of negatively charged and hydrophobic, aromatic amino acids. The absence of such patterns, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid-promoting activity of SERF2. In a protein aggregation model in the nematode C. elegans, protein aggregation was suppressed by mutating the endogenous locus of MOAG-4 to neutralize charge. Our data indicate that charge interactions are required for MOAG-4 and SERF2 to promote aggregation. Such charged interactions might accelerate the primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our finding that negatively charged segments are overrepresented in amyloid-forming proteins suggests that inhibition of charge interactions deserves exploration as a strategy to target age-related protein toxicity.Significance StatementHow aging causes relatively common diseases such as Alzheimer’s and Parkinson’s is still a mystery. Since toxic structural changes in proteins are likely to be responsible, we investigated biological mechanisms that could drive such changes. We made use of a modifying factor called SERF2, which accelerates structural changes and aggregation of several disease-related proteins. Through a peptide-binding screen, we found that SERF2 acts on negatively charged protein regions. The abundance of such regions in the disease-related proteins explains why SERF has its effect. Removing positive charge in SERF was sufficient to suppress protein aggregation in models for disease. We propose that blocking charge-interactions with SERF or other modifiers could serve as a general approach to treat age-related protein toxicity.