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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 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

The Helix-Loop-Helix motif of human EIF3A regulates translation of proliferative cellular mRNAs

Improper regulation of translation initiation, a vital checkpoint of protein synthesis in the cell, has been linked to a number of cancers. Overexpression of protein subunits of eukaryotic translation initiation factor 3 (eIF3) is associated with increased translation of mRNAs involved in cell proliferation. In addition to playing a major role in general translation initiation by serving as a scaffold for the assembly of translation initiation complexes, eIF3 regulates translation of specific cellular mRNAs and viral RNAs. Mutations in the N-terminal Helix-Loop-Helix (HLH) RNA-binding motif of the EIF3A subunit interfere with Hepatitis C Virus Internal Ribosome Entry Site (IRES) mediated translation initiation in vitro . Here we show that the EIF3A HLH motif controls translation of a small set of cellular transcripts enriched in oncogenic mRNAs, including MYC . We demonstrate that the HLH motif of EIF3A acts specifically on the 5' UTR of MYC mRNA and modulates the function of EIF4A1 on select transcripts during translation initiation. In Ramos lymphoma cell lines, which are dependent on MYC overexpression, mutations in the HLH motif greatly reduce MYC expression, impede proliferation and sensitize cells to anti-cancer compounds. These results reveal the potential of the EIF3A HLH motif in eIF3 as a promising chemotherapeutic target.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

ITeM: Independent temporal motifs to summarize and compare temporal networks

We report networks are a fundamental and flexible way of representing various complex systems. Many domains such as communication, citation, procurement, biology, social media, and transportation can be modeled as a set of entities and their relationships. Temporal networks are a specialization of general networks where every relationship occurs at a discrete time. The temporal evolution of such networks is as important to understand as the structure of the entities and relationships. We present the Independent Temporal Motif (ITeM) to characterize temporal graphs from different domains. ITeMs can be used to model the structure and the evolution of the graph. In contrast to existing work, ITeMs are edge-disjoint directed motifs that measure the temporal evolution of ordered edges within the motif. For a given temporal graph, we produce a feature vector of ITeM frequencies and the time it takes to form the ITeM instances. We apply this distribution to measure the similarity of temporal graphs. We show that ITeM has higher accuracy than other motif frequency-based approaches. We define various ITeM-based metrics that reveal salient properties of a temporal network. We also present importance sampling as a method to efficiently estimate the ITeM counts. We present a distributed implementation of the ITeM discovery algorithm using Apache Spark and GraphFrame. We evaluate our approach on both synthetic and real temporal networks.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2020

Real-time structural motif searching in proteins using an inverted index strategy

Biochemical and biological functions of proteins are the product of both the overall fold of the polypeptide chain, and, typically, structural motifs made up of smaller numbers of amino acids constituting a catalytic center or a binding site that may be remote from one another in amino acid sequence. Detection of such structural motifs can provide valuable insights into the function(s) of previously uncharacterized proteins. Technically, this remains an extremely challenging problem because of the size of the Protein Data Bank (PDB) archive. Existing methods depend on a clustering by sequence similarity and can be computationally slow. We have developed a new approach that uses an inverted index strategy capable of analyzing >170,000 PDB structures with unmatched speed. The efficiency of the inverted index method depends critically on identifying the small number of structures containing the query motif and ignoring most of the structures that are irrelevant. Our approach (implemented at motif.rcsb.org ) enables real-time retrieval and superposition of structural motifs, either extracted from a reference structure or uploaded by the user. Herein, we describe the method and present five case studies that exemplify its efficacy and speed for analyzing 3D structures of both proteins and nucleic acids.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

An evolutionarily conserved tryptophan cage promotes folding of the extended RNA recognition motif in the hnRNPR ‐like protein family

Abstract The heterogeneous nuclear ribonucleoprotein (hnRNP) R‐like family is a class of RNA binding proteins in the hnRNP superfamily with diverse functions in RNA processing. Here, we present the 1.90 Å X‐ray crystal structure and solution NMR studies of the first RNA recognition motif (RRM) of human hnRNPR. We find that this domain adopts an extended RRM (eRRM1) featuring a canonical RRM with a structured N‐terminal extension (N ext ) motif that docks against the RRM and extends the β‐sheet surface. The adjoining loop is structured and forms a tryptophan cage motif to position the N ext motif for docking to the RRM. Combining mutagenesis, solution NMR spectroscopy, and thermal denaturation studies, we evaluate the importance of residues in the N ext –RRM interface and adjoining loop on eRRM folding and conformational dynamics. We find that these sites are essential for protein solubility, conformational ordering, and thermal stability. Consistent with their importance, mutations in the N ext –RRM interface and loop are associated with several cancers in a survey of somatic mutations in cancer studies. Sequence and structure comparison of the human hnRNPR eRRM1 to experimentally verified and predicted hnRNPR‐like proteins reveals conserved features in the eRRM.

Biochemistry & Molecular Biology↗
DOE OSTI2023

Uncovering metallic glasses hidden vacancy-like motifs using machine learning

Vacancies are a ubiquitous type of defect in crystalline materials that can affect their properties and behavior, including atomic diffusivity, deformation processes, thermal conductivity, and electrical conductivity. While well-defined in crystals, it is challenging to identify such topological footprints in the amorphous structure of metallic glasses (MGs). Here, we uncover an unforeseen vacancy-like structural motif named Q7, which refers to an atomic Voronoi polyhedron with seven quadrangular faces, by investigating MG local atomic configurations with the help of machine learning. The Q7 motif exhibits characteristics similar to crystalline vacancies and plays a significant role in short-range structural disorder in MGs. The atoms at the center of the Q7 motif display larger local entropy, atomic volume, and local tension. Additionally, its concentration follows an Arrhenius-like relationship with temperature, accurately indicating the glass transition temperature, and is strongly correlated with the yield and failure of MGs during mechanical deformation. The discovery of the Q7 motif provides new insights into understanding the intricate relationship between local disorder and structural relaxation in MGs, offering a remarkable ability to predict their thermal and mechanical behavior. This potentially paves the way for enhancements in the design and manufacturing processes of MGs and other amorphous materials.

36 MATERIALS SCIENCE↗
DOE OSTI2023

A specialized integrin-binding motif enables proTGF-β2 activation by integrin αVβ6 but not αVβ8

Activation of latent transforming growth factor (TGF)-β2 is incompletely understood. Unlike TGF-β1 and β3, the TGF-β2 prodomain lacks a seven-residue RGDLXX (L/I) integrin-recognition motif and is thought not to be activated by integrins. Here, we report the surprising finding that TGF-β2 contains a related but divergent 13-residue integrin-recognition motif (YTSGDQKTIKSTR) that specializes it for activation by integrin αVβ6 but not αVβ8. Both classes of motifs compete for the same binding site in αVβ6. Multiple changes in the longer motif underlie its specificity. ProTGF-β2 structures define interesting differences from proTGF-β1 and the structural context for activation by αVβ6. Some integrin-independent activation is also seen for proTGF-β2 and even more so for proTGF-β3. Our findings have important implications for therapeutics to αVβ6 in clinical trials for fibrosis, in which inhibition of TGF-β2 activation has not been anticipated.

Science & Technology - Other Topics↗
DOE OSTI2023

Degeneracy Removal of Spin Bands in Collinear Antiferromagnets with Non–Interconvertible Spin–Structure Motif Pair

Energy bands in antiferromagnets are supposed to be spin degenerate in the absence of spin–orbit coupling (SOC). Recent studies have identified formal symmetry conditions for antiferromagnetic crystals in which this degeneracy can be lifted, spin splitting, even in the vanishing SOC (i.e., non-relativistic) limit. Materials having such symmetries could enable spin-split antiferromagnetic spintronics without the burden of using heavy-atom compounds. However, the symmetry conditions that involve spin and magnetic symmetry are not always effective as practical material selection filters. Furthermore, these symmetry conditions do not readily disclose trends in the magnitude and momentum dependence of the spin-splitting energy. Here, it is shown that the formal symmetry conditions enabling spin-split antiferromagnets can be interpreted in terms of local motif pairs, such as octahedra or tetrahedra, each carrying opposite magnetic moments. Here, collinear antiferromagnets with such a spin-structure motif pair, whose components interconvert by neither translation nor spatial inversion, will show spin splitting. Such a real-space motif-based approach enables an easy way to identify and design materials (illustrated in real example materials) having spin splitting without the need for SOC, and offers insights into the momentum dependence and magnitude of the spin splitting.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Motif-centric phosphoproteomics to target kinase-mediated signaling pathways

Identifying cellular phosphorylation pathways based on kinase-substrate relationships is a critical step to understanding the regulation of physiological functions in cells. Mass spectrometry-based phosphoproteomics workflows have made it possible to comprehensively collect information on individual phosphorylation sites in a variety of samples. However, there is still no generic approach to uncover phosphorylation networks based on kinase-substrate relationships in rare cell populations. Here, we describe a motif-centric phosphoproteomics approach combined with multiplexed isobaric labeling, in which in vitro kinase reactions are used to generate targeted phosphopeptides, which are spiked into one of the isobaric channels to increase detectability. Proof-of-concept experiments demonstrate selective and comprehensive quantification of targeted phosphopeptides by using multiple kinases for motif-centric channels. More than 7,000 tyrosine phosphorylation sites were quantified from several tens of micrograms of starting materials. This approach enables the quantification of multiple phosphorylation pathways under physiological or pathological regulation in a motif-centric manner.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Isolating the Electrocatalytic Activity of a Confined NiFe Motif within Zirconium Phosphate

Unique classes of active-site motifs are needed for improved electrocatalysis. Herein, the activity of a new catalyst motif is engineered and isolated for the oxygen evolution reaction (OER) created by nickel–iron transition metal electrocatalysts confined within a layered zirconium phosphate matrix. It is found that with optimal intercalation, confined NiFe catalysts have an order of magnitude improved mass activity compared to more conventional surface-adsorbed systems in 0.1 m KOH. Interestingly, the confined environments within the layered structure also stabilize Fe-rich compositions (90%) with exceptional mass activity compared to known Fe-rich OER catalysts. Through controls and by grafting inert molecules to the outer surface, it is evidenced that the intercalated Ni/Fe species stay within the interlayer during catalysis and serve as the active site. After determining a possible structure (wycherproofite), density functional theory is shown to correlate with the observed experimental compositional trends. It is further demonstrated that the improved activity of this motif is correlated to the Fe and water content/composition within the confined space. This work highlights the catalytic enhancement possibilities available through zirconium phosphate and isolates the activity from the intercalated species versus surface/edge ones, thus opening new avenues to develop and understand catalysts within unique nanoscale chemical environments.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Resolving complex intralayer transition motifs in high-Ni-content layered cathode materials for lithium-ion batteries

High-Ni-content layered materials are promising cathodes for next-generation lithium-ion batteries. However, investigating the atomic configurations of the delithiation-induced complex phase boundaries and their transitions remains challenging. Here, in this study, by using deep-learning-aided super-resolution electron microscopy, we resolve the intralayer transition motifs at complex phase boundaries in high-Ni cathodes. We reveal that an O3 → O1 transformation driven by delithiation leads to the formation of two types of O1–O3 interface, the continuous- and abrupt-transition interfaces. The interfacial misfit is accommodated by a continuous shear-transition zone and an abrupt structural unit, respectively. Atomic-scale simulations show that uneven in-plane Li+ distribution contributes to the formation of both types of interface, and the abrupt transition is energetically more favourable in a delithiated state where O1 is dominant, or when there is an uneven in-plane Li + distribution in a delithiated O3 lattice. Moreover, a twin-like motif that introduces structural units analogous to the abrupt-type O1–O3 interface is also uncovered. The structural transition motifs resolved in this study provide further understanding of shear-induced phase transformations and phase boundaries in high-Ni layered cathodes.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2024

Synthesis of motif and symmetry for accelerated learning, discovery, and design of electronic structures for energy conversion applications (Final Technical Report)

The overall goal of the projects is to develop a framework to incorporate structure motifs and crystal/orbital symmetries into the data-driven materials discovery infrastructure. The PI proposed to develop structure-motif- and symmetry-based graph convolutional networks for effective learning and efficient predictions of electronic structures and related properties. Fundamental understanding of the roles of structure motif and symmetry will establish new hypothesis and design rules, which will be combined with high-throughput computations based on density functional theory to discover novel light absorbers, transparent conductors, as well as 2D light emitting materials and heterojunctions for optoelectronics.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition

Protein phosphatase 2A (PP2A) holoenzymes target broad substrates by recognizing short motifs via regulatory subunits. PP2A methylesterase 1 (PME-1) is a cancer-promoting enzyme and undergoes methylesterase activation upon binding to the PP2A core enzyme. Here, we showed that PME-1 readily demethylates different families of PP2A holoenzymes and blocks substrate recognition in vitro. The high-resolution cryoelectron microscopy structure of a PP2A-B56 holoenzyme–PME-1 complex reveals that PME-1 disordered regions, including a substrate-mimicking motif, tether to the B56 regulatory subunit at remote sites. They occupy the holoenzyme substrate-binding groove and allow large structural shifts in both holoenzyme and PME-1 to enable multipartite contacts at structured cores to activate the methylesterase. B56 interface mutations selectively block PME-1 activity toward PP2A-B56 holoenzymes and affect the methylation of a fraction of total cellular PP2A. The B56 interface mutations allow us to uncover B56-specific PME-1 functions in p53 signaling. Our studies reveal multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile PME-1 activities derived from coupling substrate-mimicking motifs to dynamic structured cores.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Uncovering DNA-PKcs ancient phylogeny, unique sequence motifs and insights for human disease

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key member of the phosphatidylinositol-3 kinase-like (PIKK) family of protein kinases with critical roles in DNA-double strand break repair, transcription, metastasis, mitosis, RNA processing, and innate and adaptive immunity. The absence of DNA-PKcs from many model organisms has led to the assumption that DNA-PKcs is a vertebrate-specific PIKK. Here, we find that DNA-PKcs is widely distributed in invertebrates, fungi, plants, and protists, and that threonines 2609, 2638, and 2647 of the ABCDE cluster of phosphorylation sites are highly conserved amongst most Eukaryotes. Furthermore, we identify highly conserved amino acid sequence motifs and domains that are characteristic of DNA-PKcs relative to other PIKKs. These include residues in the Forehead domain and a novel motif we have termed YRPD, located in an α helix C-terminal to the ABCDE phosphorylation site loop. Combining sequence with biochemistry plus structural data on human DNA-PKcs unveils conserved sequence and conformational features with functional insights and implications. The defined generally progressive DNA-PKcs sequence diversification uncovers conserved functionality supported by Evolutionary Trace analysis, suggesting that for many organisms both functional sites and evolutionary pressures remain identical due to fundamental cell biology. The mining of cancer genomic data and germline mutations causing human inherited disease reveal that robust DNA-PKcs activity in tumors is detrimental to patient survival, whereas germline mutations compromising function are linked to severe immunodeficiency and neuronal degeneration. We anticipate that these collective results will enable ongoing DNA-PKcs functional analyses with biological and medical implications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

The N‐terminal intrinsically disordered region of Ncb5or docks with the cytochrome b 5 core to form a helical motif that is of ancient origin

Abstract NADH cytochromeb 5 oxidoreductase (Ncb5or) is a cytosolic ferric reductase implicated in diabetes and neurological conditions. Ncb5or comprises cytochromeb 5 (b 5 ) and cytochromeb 5 reductase (b 5 R) domains separated by a CHORD‐Sgt1 (CS) linker domain. Ncb5or redox activity depends on proper inter‐domain interactions to mediate electron transfer from NADH or NADPH via FAD to heme. While full‐length human Ncb5or has proven resistant to crystallization, we have succeeded in obtaining high‐resolution atomic structures of theb 5 domain and a construct containing the CS andb 5 R domains (CS/b 5 R). Ncb5or also contains an N‐terminal intrinsically disordered region of 50 residues that has no homologs in other protein families in animals but features a distinctive, conserved L 34 MDWIRL 40 motif also present in reduced lateral root formation (RLF) protein in rice and increased recombination center 21 in baker's yeast, all attaching to ab 5 domain. After unsuccessful attempts at crystallizing a human Ncb5or construct comprising the N‐terminal region naturally fused to theb 5 domain, we were able to obtain a high‐resolution atomic structure of a recombinant rice RLF construct corresponding to residues 25–129 of human Ncb5or (52% sequence identity; 74% similarity). The structure reveals Trp 120 (corresponding to invariant Trp 37 in Ncb5or) to be part of an 11‐residue α‐helix (S 116 QMDWLKLTRT 126 ) packing against two of the four helices in theb 5 domain that surround heme (α2 and α5). The Trp 120 side chain forms a network of interactions with the side chains of four highly conserved residues corresponding to Tyr 85 and Tyr 88 (α2), Cys 124 (α5), and Leu 47 in Ncb5or. Circular dichroism measurements of human Ncb5or fragments further support a key role of Trp 37 in nucleating the formation of the N‐terminal helix, whose location in the N/b 5 module suggests a role in regulating the function of this multi‐domain redox enzyme. This study revealed for the first time an ancient origin of a helical motif in the N/b 5 module as reflected by its existence in a class of cytochromeb 5 proteins from three kingdoms among eukaryotes.

Biochemistry & Molecular Biology↗
DOE OSTI2024

Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif

ABSTRACT Avian influenza viruses are ubiquitous in the Anatinae subfamily of aquatic birds and occasionally spill over to poultry. Infection with low pathogenicity avian influenza viruses generally leads to subclinical or mild clinical disease. In contrast, highly pathogenic avian influenza viruses emerge from low pathogenic forms and can cause severe disease associated with extraordinarily high mortality rates. Here, we describe the natural history of avian influenza virus, with a focus on H5Nx and H7Nx subtypes, and the emergence of highly pathogenic forms; we review the biology of AIV; we examine cleavage of haemagglutinin by host cell enzymes with a particular emphasis on the biochemical properties of the proprotein convertases, and trypsin and trypsin‐like proteases; we describe mechanisms implicated in the functional evolution of the haemagglutinin cleavage site motif that leads to emergence of HPAIVs; and finally, we discuss the diversity of H5 and H7 haemagglutinin cleavage site sequence motifs. It is crucial to understand the molecular attributes that drive the emergence and evolution of HPAIVs with pandemic potential to inform risk assessments and mitigate the threat of HPAIVs to poultry and human populations.

Luczo, Jasmina M. [Australian Animal Health Labora↗
DOE OSTI2026

First-Principles Evaluation of Proton Hopping in Tetrahedral Oxide Motifs

Proton-conducting oxides (PCOs) are important materials used as ionic conductors for energy conversion technologies. Existing research efforts on PCO optimization and discovery generally focus on complex perovskite-based oxides that require doping and alloying to engineer oxygen deficiency and high proton conductivity. However, the variety of chemical compositions and coordination environments in oxides poses challenges for efficient materials design. In this computational study, we construct a database of simplified motifs to elucidate the relationship between fundamental materials chemistry and proton kinetics. Specifically, we focus on the zincblende crystal structure as a proxy for tetrahedral metal–oxide (M–O) coordination environments. We systematically quantified the effects of cation type, oxidation states, and M–O bond lengths on the proton hopping barrier, and found that strong M–O bonds and metal cations with large and variable oxidation states (e.g., Mo 6+ , V 5+ ) lead to smaller proton hopping barriers. By mapping the candidate cations and their preferred bond geometries onto materials databases such as the Inorganic Crystal Structure Database (ICSD) and Materials Project, we identified real materials containing the corresponding metal–oxide units. In general, we observed good agreement between the calculated proton hopping barriers obtained in real crystal structures and those predicted by our motif database. We also discuss the limitations of our model and possible future extensions to improve its predictive capabilities. Overall, our model provides a first step for the rational design and quick screening of energy-efficient PCOs.

organic↗
DOE OSTI2024

Accurate, Uncertainty-Aware Classification of Molecular Chemical Motifs from Multimodal X-ray Absorption Spectroscopy

Accurate classification of molecular chemical motifs from experimental measurement is an important problem in molecular physics, chemistry, and biology. In this work, we present neural network ensemble classifiers for predicting the presence (or lack thereof) of 41 different chemical motifs on small molecules from simulated C, N, and O K-edge X-ray absorption near-edge structure (XANES) spectra. Our classifiers not only achieve class-balanced accuracies of more than 0.95 but also accurately quantify uncertainty. Here, we also show that including multiple XANES modalities improves predictions notably on average, demonstrating a “multimodal advantage” over any single modality. In addition to structure refinement, our approach can be generalized to broad applications with molecular design pipelines.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Novel Structural Motif To Promote Mg-Ion Mobility: Investigating ABO 4 Zircons as Magnesium Intercalation Cathodes

There is an increasing need for sustainable energy storage solutions as fossil fuels are replaced by renewable energy sources. Multivalent batteries, specifically Mg batteries, are one energy storage technology that researchers continue to develop with hopes to surpass the performance of Li-ion batteries. However, the limited energy density and transport properties of Mg cathodes remain critical challenges preventing the realization of high-performance multivalent batteries. In this work, ABO 4 zircon materials (A = Y, Eu and B = V, Cr) are computationally and experimentally evaluated as Mg intercalation cathodes. Remarkably good Mg-ion transport properties were predicted and Mg-ion intercalation was experimentally verified in sol-gel synthesized zircon YVO 4 , EuVO 4 , and EuCrO 4 . Among them, EuVO 4 exhibited the best electrochemical performance and demonstrated repeated reversible cycling. While we believe that the one-dimensional diffusion channels and redox-active species tetragonal coordination limit the value of many zircons as high-performance cathodes, their unique structural motif of overlapping polyhedra along the diffusion pathway appears instrumental for promoting good Mg-ion mobility. The motif results in a favorable "6-5-4" change in coordination that avoids unfavorable sites with lower coordination along the diffusion pathway and a structural design metric for future Mg cathode development.

25 ENERGY STORAGE↗