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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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At least 1,747 records · Page 97
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Development of a universal nanobody-binding Fab module for fiducial-assisted cryo-EM studies of membrane proteins

Structural studies of membrane proteins by cryogenic electron microscopy (cryo-EM) often require antibody fragments (Fabs) to facilitate particle alignments and achieve high resolution. While conformational nanobodies have been developed to lock specific states of many membrane proteins, they only add 15 kDa of mass to the complex. We developed a synthetic Fab (NabFab) that rigidly binds the conserved scaffold of nanobodies, providing a universally applicable fiducial for cryo-EM studies of protein–nanobody complexes. Additionally, we demonstrate the concept by determining two high-resolution structures of membrane proteins bound to specific nanobodies and NabFab. As the structural epitope for NabFab can be incorporated into the scaffold of virtually any nanobody, this raises the prospect of facile structure determination of many nanobody–protein complexes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Surface coating by mechanofusion modulates bulk charging pathways and battery performance of Ni-rich layered cathodes

Ni-rich layered oxides as high-capacity battery cathodes suffer from degradation at high voltages. Here, we utilize a dry surface modification method, mechanofusion (MF), to achieve enhanced battery stability. The simplicity, high yield, and flexibility make it cost-effective and highly attractive for processing at the industrial scale. The underlying mechanisms responsible for performance improvement are unveiled by a systematic study combining multiple probes, e.g., 3D nano-tomography, spectroscopic imaging, in situ synchrotron diffraction, and finite element analysis (FEA). MF affects the bulk crystallography by introducing partially disordered structure, microstrain, and local lattice variation. Furthermore, the crack initiation and propagation pattern during delithiation are regulated and the overall mechanical fracture is reduced after such surface coating. We validate that MF can alter the bulk charging pathways. Such a synergic effect between surface modification and bulk charge distribution is fundamentally important for designing next-generation battery cathode materials.

25 ENERGY STORAGE↗
DOE OSTI2023

Modulation of xanthophyll cycle impacts biomass productivity in the marine microalga Nannochloropsis

Life on earth depends on photosynthetic primary producers that exploit sunlight to fix CO 2 into biomass. Approximately half of global primary production is associated with microalgae living in aquatic environments. Microalgae also represent a promising source of biomass to complement crop cultivation, and they could contribute to the development of a more sustainable bioeconomy. Photosynthetic organisms evolved multiple mechanisms involved in the regulation of photosynthesis to respond to highly variable environmental conditions. While essential to avoid photodamage, regulation of photosynthesis results in dissipation of absorbed light energy, generating a complex trade-off between protection from stress and light-use efficiency. This work investigates the impact of the xanthophyll cycle, the light-induced reversible conversion of violaxanthin into zeaxanthin, on the protection from excess light and on biomass productivity in the marine microalgae of the genus Nannochloropsis. Zeaxanthin is shown to have an essential role in protection from excess light, contributing to the induction of nonphotochemical quenching and scavenging of reactive oxygen species. On the contrary, the overexpression of zeaxanthin epoxidase enables a faster reconversion of zeaxanthin to violaxanthin that is shown to be advantageous for biomass productivity in dense cultures in photobioreactors. These results demonstrate that zeaxanthin accumulation is critical to respond to strong illumination, but it may lead to unnecessary energy losses in light-limiting conditions and accelerating its reconversion to violaxanthin provides an advantage for biomass productivity in microalgae.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structure-guided approach to modulate small molecule binding to a promiscuous ligand-activated protein

Ligand-binding promiscuity in detoxification systems protects the body from toxicological harm but is a roadblock to drug development due to the difficulty in optimizing small molecules to both retain target potency and avoid metabolic events. Immense effort is invested in evaluating metabolism of molecules to develop safer, more effective treatments, but engineering specificity into or out of promiscuous proteins and their ligands is a challenging task. To better understand the promiscuous nature of detoxification networks, we have used X-ray crystallography to characterize a structural feature of pregnane X receptor (PXR), a nuclear receptor that is activated by diverse molecules (with different structures and sizes) to up-regulate transcription of drug metabolism genes. We found that large ligands expand PXR’s ligand-binding pocket, and the ligand-induced expansion occurs through a specific unfavorable compound-protein clash that likely contributes to reduced binding affinity. Removing the clash by compound modification resulted in more favorable binding modes with significantly enhanced binding affinity. We then engineered the unfavorable ligand-protein clash into a potent, small PXR ligand, resulting in marked reduction in PXR binding and activation. Structural analysis showed that PXR is remodeled, and the modified ligands reposition in the binding pocket to avoid clashes, but the conformational changes result in less favorable binding modes. Thus, ligand-induced binding pocket expansion increases ligand-binding potential of PXR but is an unfavorable event; therefore, drug candidates can be engineered to expand PXR’s ligand-binding pocket and reduce their safety liability due to PXR binding.

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

Modulating metal-centered dimerization of a lanthanide chaperone protein for separation of light lanthanides

Elucidating details of biology’s selective uptake and trafficking of rare earth elements, particularly the lanthanides, has the potential to inspire sustainable biomolecular separations of these essential metals for myriad modern technologies. Here, we biochemically and structurally characterize Methylobacterium (Methylorubrum) extorquens LanD, a periplasmic protein from a bacterial gene cluster for lanthanide uptake. This protein provides only four ligands at its surface-exposed lanthanide-binding site, allowing for metal-centered protein dimerization that favors the largest lanthanide, La III . However, the monomer prefers Nd III and Sm III , which are disfavored lanthanides for cellular utilization. Structure-guided mutagenesis of a metal-ligand and an outer-sphere residue weakens metal binding to the LanD monomer and enhances dimerization for Pr III and Nd III by 100-fold. Selective dimerization enriches high-value Pr III and Nd III relative to low-value La III and Ce III in an all-aqueous process, achieving higher separation factors than lanmodulins and comparable or better separation factors than common industrial extractants. Finally, we show that LanD interacts with lanmodulin (LanM), a previously characterized periplasmic protein that shares LanD’s preference for Nd III and Sm III . Our results suggest that LanD’s unusual metal-binding site transfers less-desirable lanthanides to LanM to siphon them away from the pathway for cytosolic import. The properties of LanD show how relatively weak chelators can achieve high selectivity, and they form the basis for the design of protein dimers for separation of adjacent lanthanide pairs and other metal ions.

lanthanide biochemistry↗
DOE OSTI2025

Enhanced chloroplast FtsZ-ring constriction by the ARC6–ARC3 module in Arabidopsis

Chloroplast division, a process tightly linked to the energy demands of plants, is initiated by the formation of the stromal filamenting temperature-sensitive Z (FtsZ) ring. The Z ring is highly dynamic, and its constriction provides the essential force for chloroplast division. However, the regulatory mechanisms governing Z-ring dynamics and constriction remain poorly understood. Here, we report that the chloroplast inner envelope membrane (IEM) protein ACCUMULATION AND REPLICATION OF CHLOROPLASTS6 (ARC6) interacts with the chloroplast stromal protein ARC3, and this interaction is negatively regulated by the conserved J-like domain of ARC6. ARC3 is found both distributed throughout the stroma and localized to a ring-like structure at the chloroplast division site. We demonstrate that ARC6 recruits ARC3 to the division site to form a ring-like structure, likely through direct interaction. This ARC6–ARC3 interaction enables ARC3 to bind FtsZs. Furthermore, we show that the ARC6–ARC3 complex significantly promotes the dynamics of chloroplast Z rings reconstituted in a heterologous system. Finally, the constriction of these reconstituted Z rings is markedly enhanced by ARC6–ARC3. Our findings reveal a regulatory mechanism that governs Z-ring dynamics and constriction, shedding light on the molecular mechanisms underlying chloroplast division.

Science & Technology - Other Topics↗
DOE OSTI2025

Water content modulation enables selective ion transport in 2D MXene membranes

Separation membranes are critical for a range of processes, including but not limited to water desalination, chemical and fuel production, and recycling and recovery applications. Fundamentally, there are intrinsic trade-offs between permeability and selectivity. Local water organization and content can impact membrane structure (short- and long-range) in laminar transition metal carbide (MXene) membranes and impact selective ion permeation. Intercalation of chaotropic cesium (Cs + ) ions within the layers reduces the water content in the membrane and at the surface which cannot be found in the intercalation of other ions. Additionally, 3D imaging using focused ion beam scanning electron microscopy showed fewer defects in the Cs-MXene membrane, due to reduced local water content, leading to more efficient ion sieving. X-ray diffraction and density functional theory calculations on the nanochannel structure demonstrated that the chaotropic ion results in the smallest nanochannel size and induces a stronger resistance to water-induced nanochannel swelling. With a narrower nanochannel, the Cs-MXene membrane limits ion transport pathways, resulting in more selective transport of lithium over other metal cations, as evidenced in both experiment and molecular dynamics simulations. In conclusion, our findings highlight the potential for controlling the structural organization of 2D MXene membranes to enable on-demand transport of ions for diverse applications.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Tandem sialoglycan-binding modules in a Streptococcus sanguinis serine-rich repeat adhesin create target dependent avidity effects

Sialic acid–binding immunoglobulin-like lectins (Siglec)–like domains of streptococcal serine-rich repeat (SRR) adhesins recognize sialylated glycans on human salivary, platelet, and plasma glycoproteins via a YTRY sequence motif. The SRR adhesin from Streptococcus sanguinis strain SK1 has tandem sialoglycan-binding domains and has previously been shown to bind sialoglycans with high affinity. However, both domains contain substitutions within the canonical YTRY motif, making it unclear how they interact with host receptors. To identify how the S. sanguinis strain SK1 SRR adhesin affects interactions with sialylated glycans and glycoproteins, we determined high-resolution crystal structures of the binding domains alone and with purified trisaccharides. These structural studies determined that the ligands still bind at the noncanonical binding motif, but with fewer hydrogen-bonding interactions to the protein than is observed in structures of other Siglec-like adhesins. Complementary biochemical studies identified that each of the two binding domains has a different selectivity profile. Interestingly, the binding of SK1 to platelets and plasma glycoproteins identified that the interaction to some host targets is dominated by the contribution of one binding domain, whereas the binding to other host receptors is mediated by both binding domains. These results provide insight into outstanding questions concerning the roles of tandem domains in targeting host receptors and suggest mechanisms for how pathogens can adapt to the availability of a range of related but nonidentical host receptors. They further suggest that the definition of the YTRY motif should be changed to ΦTRX, a more rigorous description of this sialic acid–recognition motif given recent findings.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults

Xanthohumol (XN), a polyphenol found in the hop plant (Humulus lupulus), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN’s impact on human gut microbiota in vivo. We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) to determine safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were enterotype-dependent. These results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Disentangling the mechanism of temperature and water vapor modulation on ozone under a warming climate

Temperature and water vapor have been considered as important factors affecting ozone concentrations, however, their synergistic effect on ozone, as well as its response to a warming climate remains unclear. Here, numerical experiments with different combinations of climate and emissions highlighted opposite changes of annual ozone over the contiguous U.S. under scenarios with high vs. low ozone precursor emissions in the future with warming. Comparing the occurrence of heat waves on higher vs. lower ozone days, we found significant suppression of the heat wave exacerbation of ozone by anthropogenic emissions reductions. Variations of ozone with temperature (T) and water vapor (Q) over the western U.S. and southeastern U.S. in the simulations are clearly revealed through the construction of an O 3 -T-Q diagram. Based on the diagram, we further identified a T-dominant regime at higher temperatures where ozone increases with temperature increase, and a Q-dominant regime at lower temperatures where ozone decreases with temperature increase due to the negative effect of water vapor. With larger anthropogenic emission reductions, ozone may increase at a lower rate with temperature in the T-dominant regime, or even decrease with temperature in the Q-dominant regime. Our results show that with large emission reductions, substantial ozone pollution due to warming and increasing heat waves may be counteracted by water vapor, partly turning the ‘climate penalty’ on ozone into ‘climate benefit’. Hence controlling anthropogenic emissions may be an increasingly important strategy in a warmer and wetter climate to improve air quality and public health.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

RCSB Protein Data Bank 1D3D module: displaying positional features on macromolecular assemblies

Mapping positional features from one-dimensional (1D) sequences onto three-dimensional (3D) structures of biological macromolecules is a powerful tool to show geometric patterns of biochemical annotations and provide a better understanding of the mechanisms underpinning protein and nucleic acid function at the atomic level. We present a new library designed to display fully customizable interactive views between 1D positional features of protein and/or nucleic acid sequences and their 3D structures as isolated chains or components of macromolecular assemblies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

O-GlcNAc transferase Ogt regulates embryonic neuronal development through modulating Wnt/β-catenin signaling

Abstract Ogt-mediated O-GlcNAcylation is enriched in the nervous system and involves in neuronal development, brain function and neurological diseases. However, the roles of Ogt and O-GlcNAcylation in embryonic neurogenesis have remained largely unknown. Here, we show that Ogt is highly expressed in embryonic brain, and Ogt depletion reduces the proliferation of embryonic neural stem cells and migration of new born neurons. Ogt depletion in cultured hippocampal neurons impairs neuronal maturation, including reduced dendritic numbers and length, and immature development of spines. Mechanistically, Ogt depletion decreases the activity of Wnt/β-catenin signaling. Ectopic β-catenin rescues neuronal developmental deficits caused by Ogt depletion. Ogt also regulates human cortical neurogenesis in forebrain organoids derived from induced pluripotent stem cells. Our findings reveal the essential roles and mechanisms of Ogt-mediated O-GlcNAc modification in regulating mammalian neuronal development.

Shen, Hui↗
DOE OSTI2025

Climate history modulates stress responses of common soil bacteria under experimental drought

Soil drying challenges microbial viability and survival, with bacteria employing various mechanisms to respond to shifts in osmolarity, including dormancy or metabolic upregulation of osmoprotectants. However, the extent to which these responses are shaped by an organism's phylogeny, or the climate history of a given environment is poorly understood. This study examines the responses of phylogenetically similar bacteria from semi-arid and humid tropical forest soils to osmotic and matric stress using synchrotron radiation-based Fourier Transform Infrared spectromicroscopy. This non-destructive approach depicts the biochemical phenotype for whole cells under control and stress conditions. We observed that, under osmotic stress, bacteria upregulated cell-signaling pathways, rapidly turned over lipid-storage compounds, and increased osmolyte production. In contrast, matric stress induced a more muted response, typically elevating the production of carbohydrate stress compounds, such as glycine betaine and trehalose. Whereas phylogenetically similar bacteria showed comparable biochemistry under control conditions, climate history played an important role in regulating responses to stress, whereby a stronger metabolic response was observed from semi-arid relative to tropical forest isolates. We conclude that bacterial stress response to drought can be more diverse than previously observed and regulated by both phylogeny and climate history.

54 ENVIRONMENTAL SCIENCES↗