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Results for “calcium-binding protein”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Ca X ML: Chemistry‐informed machine learning explains mutual changes between protein conformations and calcium ions in calcium‐binding proteins using structural and topological features

Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes. However, it is unclear whether the limited experimental data available can be effectively used to train models to accurately predict the charges of calcium-binding protein variants. Here, we developed a chemistry-informed, machine-learning algorithm that implements a game theoretic approach to explain the output of a machine-learning model without the prerequisite of an excessively large database for high-performance prediction of atomic charges. We used the ab initio electronic structure data representing calcium ions and the structures of the disordered segments of calcium-binding peptides with surrounding water molecules to train several explainable models. Network theory was used to extract the topological features of atomic interactions in the structurally complex data dictated by the coordination chemistry of a calcium ion, a potent indicator of its charge state in protein. Our design created a computational tool of Ca X ML, which provided a framework of explainable machine learning model to annotate ionic charges of calcium ions in calcium-binding proteins in response to the chemical changes in an environment. Our framework will provide new insights into protein design for engineering functionality based on the limited size of scientific data in a genome space.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Lanthanide binding peptide surfactants at air–aqueous interfaces for interfacial separation of rare earth elements

Rare earth elements (REEs) are critical materials to modern technologies. They are obtained by selective separation from mining feedstocks consisting of mixtures of their trivalent cation. We are developing an all-aqueous, bioinspired, interfacial separation using peptides as amphiphilic molecular extractants. Lanthanide binding tags (LBTs) are amphiphilic peptide sequences based on the EF-hand metal binding loops of calcium-binding proteins which complex selectively REEs. We study LBTs optimized for coordination to Tb 3+ using luminescence spectroscopy, surface tensiometry, X-ray reflectivity, and X-ray fluorescence near total reflection, and find that these LBTs capture Tb 3+ in bulk and adsorb the complex to the interface. Molecular dynamics show that the binding pocket remains intact upon adsorption. We find that, if the net negative charge on the peptide results in a negatively charged complex, excess cations are recruited to the interface by nonselective Coulombic interactions that compromise selective REE capture. If, however, the net negative charge on the peptide is −3, resulting in a neutral complex, a 1:1 surface ratio of cation to peptide is achieved. Surface adsorption of the neutral peptide complexes from an equimolar mixture of Tb 3+ and La 3+ demonstrates a switchable platform dictated by bulk and interfacial effects. The adsorption layer becomes enriched in the favored Tb 3+ when the bulk peptide is saturated, but selective to La 3+ for undersaturation due to a higher surface activity of the La 3+ complex.

Ortuno Macias, Luis E. (ORCID:0000000284342192)↗
DOE OSTI2026

Molecular pathways for learning in the single-cell Stentor coeruleus

The single-cell Stentor coeruleus contracts in response to mechanical taps but habituates and learns to ignore the taps after repeated stimulation. Here, we explored the molecular changes that occur during the formation of this cellular memory in order to improve our understanding of non-synaptic learning. We impaired cellular protein synthesis with cycloheximide and puromycin and found that, contrary to the effects of such treatments on metazoa, these drugs accelerate habituation and prolong memory retention in Stentor . Exploratory proteomic and transcriptomic analyses identified candidate proteins and genes that changed over the course of habituation and response recovery, pointing toward the regulation of Stentor learning by calcium signaling and protein phosphorylation. Building on these results, we found that using RNA interference to knock down the calcium-binding, EF-hand domain-containing protein SteCoe_6763 accelerated habituation. Furthermore, increased extracellular calcium improved Stentor learning, while treatment with kinase and phosphatase inhibitors impaired learning. In particular, KN-93, a drug known to inhibit calcium/calmodulin-dependent kinase II and voltage-gated calcium channels, decreased both the rate and extent of habituation in Stentor , similar to its effects on learning in metazoa. We also discovered that habituation memory can be maintained in progeny following cell division. Taken together, these results suggest that response recovery in Stentor requires new protein synthesis and that memory formation involves the modification of delocalized mechanoreceptors by phosphorylation and calcium signaling. This is consistent with our previous model of Stentor learning, in which habituation occurs through the inactivation of cell-surface receptors.

CaMKII↗
DOE OSTI2024

Sequence-defined structural transitions by calcium-responsive proteins

Biopolymer sequences dictate their functions, and protein-based polymers are a promising platform to establish sequence–function relationships for novel biopolymers. To efficiently explore vast sequence spaces of natural proteins, sequence repetition is a common strategy to tune and amplify specific functions. This strategy is applied to repeats-in-toxin (RTX) proteins with calcium-responsive folding behavior, which stems from tandem repeats of the nonapeptide GGXGXDXUX in which X can be any amino acid and U is a hydrophobic amino acid. To determine the functional range of this nonapeptide, we modified a naturally occurring RTX protein that forms β-roll structures in the presence of calcium. Sequence modifications focused on calcium-binding turns within the repetitive region, including either global substitution of nonconserved residues or complete replacement with tandem repeats of a consensus nonapeptide GGAGXDTLY. Some sequence modifications disrupted the typical transition from intrinsically disordered random coils to folded β rolls, despite conservation of the underlying nonapeptide sequence. Proteins enriched with smaller, hydrophobic amino acids adopted secondary structures in the absence of calcium and underwent structural rearrangements in calcium-rich environments. In contrast, proteins with bulkier, hydrophilic amino acids maintained intrinsic disorder in the absence of calcium. In conclusion, these results indicate a significant role of nonconserved amino acids in calcium-responsive folding, thereby revealing a strategy to leverage sequences in the design of tunable, calcium-responsive biopolymers.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗