The interpretation of a salt's effect on protein stability traditionally discriminates low concentration regimes (<0.3 M), dominated by electrostatic forces, and high concentration regimes, generally described by ion-specific Hofmeister effects. However, increased theoretical and experimental studies have highlighted observations of the Hofmeister phenomena at concentration ranges as low as 0.001 M. Reasonable quantitative predictions of such observations have been successfully achieved throughout the inclusion of ion dispersion forces in classical electrostatic theories. This molecular description is also on the basis of quantitative estimates obtained resorting to surface/bulk solvent partition models developed for ion-specific Hofmeister effects. However, the latter are limited by the availability of reliable structures representative of the unfolded state. Here, we use myoglobin as a model to explore how ion-dependency on the nature of the unfolded state affects protein stability, combining spectroscopic techniques with molecular dynamic simulations. To this end, the thermal and chemical stability of myoglobin was assessed in the presence of three different salts (NaCl, (NH)SO and NaSO), at physiologically relevant concentrations (0-0.3 M). We observed mild destabilization of the native state induced by each ion, attributed to unfavorable neutralization and hydrogen-bonding with the protein side-chains. Both effects, combined with binding of Na, Cl and SO to the thermally unfolded state, resulted in an overall destabilization of the protein. Contrastingly, ion binding was hindered in the chemically unfolded conformation, due to occupation of the binding sites by urea molecules. Such mechanistic action led to a lower degree of destabilization, promoting surface tension effects that stabilized myoglobin according to the Hofmeister series. Therefore, we demonstrate that Hofmeister effects on protein stability are modulated by the heterogeneous physico-chemical nature of the unfolded state. Altogether, our findings evidence the need to characterize the structure of the unfolded state when attempting to dissect the molecular mechanisms underlying the effects of salts on protein stability.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1039/d1cp02477a | DOI Listing |
J Med Virol
December 2024
Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
SARS-CoV-2 continues to mutate, leading to breakthrough infections. The development of new vaccine strategies to combat various strains is crucial. Protein cyclization can enhance thermal stability and may improve immunogenicity.
View Article and Find Full Text PDFG3 (Bethesda)
December 2024
Department of Integrative Biology, University of Guelph, Guelph, Ontario, N1G 2W1.
The release of heavy metals from industrial, agricultural, and mining activities poses significant risks to aquatic ecosystems by degrading water quality and generating reactive oxygen species (ROS) that can damage DNA in aquatic organisms. Daphnia is a widespread keystone species in freshwater ecosystems that is routinely exposed to a range of anthropogenic and natural stressors. With a fully sequenced genome, a well-understood life history and ecology, and an extensive library of responses to toxicity, Daphnia serves as an ideal model organism for studying the impact of environmental stressors on genomic stability.
View Article and Find Full Text PDFZhonghua Yu Fang Yi Xue Za Zhi
December 2024
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu610041, China.
Bones possess metabolic activity, with their homeostasis maintained by bone resorption and bone formation mediated by osteoclasts and osteoblasts. By measuring bone metabolism markers, the overall state of bone metabolism and dynamic changes in systemic bone tissue can be reflected. Traditional bone turnover markers, including alkaline phosphatase, bonespecific alkaline phosphatase, procollagen type 1 N-terminal propeptide, procollagen type 1 C-terminal propeptide, osteocalcin, c-terminal telopeptides of type 1 collagen(CTX) and its subtype β-CTX, n-terminal telopeptides of type 1 collagen, have been widely used in clinical practice but still have limitations in terms of stability, diagnostic reliability, and specific reflection of bone sites.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA. Electronic address:
Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) promotes fetal and placental growth and development, with MAP3K4 kinase inactivation resulting in placental insufficiency and fetal growth restriction. MAP3K4 promotes key signaling pathways including JNK, p38, and PI3K/Akt, leading to activation of CREB-binding protein. MAP3K4 kinase inactivation results in loss of these pathways and gain of histone deacetylase 6 (HDAC6) expression and activity.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL, USA. Electronic address:
The sarco(endo)plasmic reticulum Ca ATPase (SERCA) is a membrane transporter that creates and maintains intracellular Ca stores. In the heart, SERCA is regulated by an inhibitory interaction with the monomeric form of the transmembrane micropeptide phospholamban (PLB). PLB also forms avid homo-pentamers, and dynamic exchange of PLB between pentamers and SERCA is an important determinant of cardiac responsiveness to exercise.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!