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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 199 records · Page 11
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin

The naturally occurring nucleotide 2-deoxy-adenosine 5'-triphosphate (dATP) can be used by cardiac muscle as an alternative energy substrate for myosin chemomechanical activity. We and others have previously shown that dATP increases contractile force in normal hearts and models of depressed systolic function, but the structural basis of these effects has remained unresolved. In this work, we combine multiple techniques to provide structural and functional information at the angstrom-nanometer and millisecond time scales, demonstrating the ability to make both structural measurements and quantitative kinetic estimates of weak actin–myosin interactions that underpin sarcomere dynamics. Exploiting dATP as a molecular probe, we assess how small changes in myosin structure translate to electrostatic-based changes in sarcomere function to augment contractility in cardiac muscle. Through Brownian dynamics simulation and computational structural analysis, we found that deoxy-hydrolysis products [2-deoxy-adenosine 5′-diphosphate (dADP) and inorganic phosphate (Pi)] bound to prepowerstroke myosin induce an allosteric restructuring of the actin-binding surface on myosin to increase the rate of cross-bridge formation. We then show experimentally that this predicted effect translates into increased electrostatic interactions between actin and cardiac myosin in vitro. Finally, using small-angle X-ray diffraction analysis of sarcomere structure, we demonstrate that the proposed increased electrostatic affinity of myosin for actin causes a disruption of the resting conformation of myosin motors, resulting in their repositioning toward the thin filament before activation. The dATP-mediated structural alterations in myosin reported here may provide insight into an improved criterion for the design or selection of small molecules to be developed as therapeutic agents to treat systolic dysfunction.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Growth on ATP elicits a P-stress response in the picoeukaryote Micromonas pusilla

The surface waters of oligotrophic oceans have chronically low phosphate (P i ) concentrations, which renders dissolved organic phosphorus (DOP) an important nutrient source. In the subtropical North Atlantic, cyanobacteria are often numerically dominant, but picoeukaryotes can dominate autotrophic biomass and productivity making them important contributors to the ocean carbon cycle. Despite their importance, little is known regarding the metabolic response of picoeukaryotes to changes in phosphorus (P) source and availability. To understand the molecular mechanisms that regulate P utilization in oligotrophic environments, we evaluated transcriptomes of the picoeukaryote Micromonas pusilla grown under P i -replete and -deficient conditions, with an additional investigation of growth on DOP in replete conditions. Genes that function in sulfolipid substitution and P i uptake increased in expression with P i -deficiency, suggesting cells were reallocating cellular P and increasing P acquisition capabilities. P i -deficient M. pusilla cells also increased alkaline phosphatase activity and reduced their cellular P content. Cells grown with DOP were able to maintain relatively high growth rates, however the transcriptomic response was more similar to the P i -deficient response than that seen in cells grown under P i -replete conditions. The results demonstrate that not all P sources are the same for growth; while M. pusilla , a model picoeukaryote, may grow well on DOP, the metabolic demand is greater than growth on P i . Lastly, these findings provide insight into the cellular strategies which may be used to support growth in a stratified future ocean predicted to favor picoeukaryotes.

59 BASIC BIOLOGICAL SCIENCES↗