Observation of Coherently Coupled Cation Spin Dynamics in an Insulating Ferrimagnetic Oxide

Many technologically useful magnetic oxides are ferrimagnetic insulators, which consist of chemically distinct cations. Here, we examine the spin dynamics of different magnetic cations in ferrimagnetic NiZnAl-ferrite (Ni$_{0.65}$Zn$_{0.35}$Al$_{0.8}$Fe$_{1.2}$O$_4$) under continuous microwave excitation. Specifically, we employ time-resolved x-ray ferromagnetic resonance to separately probe Fe$^{2+/3+}$ and Ni$^{2+}$ cations on different sublattice sites. Our results show that the precessing cation moments retain a rigid, collinear configuration to within $\approx$2$^\circ$. Moreover, the effective spin relaxation is identical to within $<$10% for all magnetic cations in the ferrite. We thus validate the oft-assumed ``ferromagnetic-like'' dynamics in resonantly driven ferrimagnetic oxides, where the magnetic moments from different cations precess as a coherent, collective magnetization

Probing the Interaction of the Diarylquinoline TMC207 with Its Target Mycobacterial ATP Synthase

Infections with Mycobacterium tuberculosis are substantially increasing on a worldwide scale and new antibiotics are urgently needed to combat concomitantly emerging drug-resistant mycobacterial strains. The diarylquinoline TMC207 is a highly promising drug candidate for treatment of tuberculosis. This compound kills M. tuberculosis by binding to a new target, mycobacterial ATP synthase. In this study we used biochemical assays and binding studies to characterize the interaction between TMC207 and ATP synthase. We show that TMC207 acts independent of the proton motive force and does not compete with protons for a common binding site. The drug is active on mycobacterial ATP synthesis at neutral and acidic pH with no significant change in affinity between pH 5.25 and pH 7.5, indicating that the protonated form of TMC207 is the active drug entity. The interaction of TMC207 with ATP synthase can be explained by a one-site binding mechanism, the drug molecule thus binds to a defined binding site on ATP synthase. TMC207 affinity for its target decreases with increasing ionic strength, suggesting that electrostatic forces play a significant role in drug binding. Our results are consistent with previous docking studies and provide experimental support for a predicted function of TMC207 in mimicking key residues in the proton transfer chain and blocking rotary movement of subunit c during catalysis. Furthermore, the high affinity of TMC207 at low proton motive force and low pH values may in part explain the exceptional ability of this compound to efficiently kill mycobacteria in different microenvironments

A New Type of Proton Coordination in an F1Fo-ATP Synthase Rotor Ring

The high-resolution structure of the rotor ring from alkaliphilic Bacillus pseudofirmus OF4 reveals a new type of ion binding in F1Fo-ATP synthases

Highly Divergent Mitochondrial ATP Synthase Complexes in Tetrahymena thermophila

Tetrahymena ATP synthase, an evolutionarily divergent protein complex, has a very unusual structure and protein composition including a unique Fo subunit a and at least 13 proteins with no orthologs outside of the ciliate lineage

Genomics of alkaliphiles

Alkalinicity presents a challenge for life due to a “reversed” proton gradient that is unfavourable to many bioenergetic processes across the membranes of microorganisms. Despite this, many bacteria, archaea, and eukaryotes, collectively termed alkaliphiles, are adapted to life in alkaline ecosystems and are of great scientific and biotechnological interest due to their niche specialization and ability to produce highly stable enzymes. Advances in next-generation sequencing technologies have propelled not only the genomic characterization of many alkaliphilic microorganisms that have been isolated from nature alkaline sources but also our understanding of the functional relationships between different taxa in microbial communities living in these ecosystems. In this review, we discuss the genetics and molecular biology of alkaliphiles from an “omics” point of view, focusing on how metagenomics and transcriptomics have contributed to our understanding of these extremophiles.https://link.springer.com/bookseries/10hj2021BiochemistryGeneticsMicrobiology and Plant Patholog

On the principle of ion selectivity in Na⁺/H⁺-coupled membrane proteins: Experimental and theoretical studies of an ATP synthase rotor

Numerous membrane transporters and enzymes couple their mechanisms to the permeation of Na(+) or H(+), thereby harnessing the energy stored in the form of transmembrane electrochemical potential gradients to sustain their activities. The molecular and environmental factors that control and modulate the ion specificity of most of these systems are, however, poorly understood. Here, we use isothermal titration calorimetry to determine the Na(+)/H(+) selectivity of the ion-driven membrane rotor of an F-type ATP synthase. Consistent with earlier theoretical predictions, we find that this rotor is significantly H(+) selective, although not sufficiently to be functionally coupled to H(+), owing to the large excess of Na(+) in physiological settings. The functional Na(+) specificity of this ATP synthase thus results from two opposing factors, namely its inherent chemical selectivity and the relative availability of the coupling ion. Further theoretical studies of this membrane rotor, and of two others with a much stronger and a slightly weaker H(+) selectivity, indicate that, although the inherent selectivity of their ion-binding sites is largely set by the balance of polar and hydrophobic groups flanking a conserved carboxylic side chain, subtle variations in their structure and conformational dynamics, for a similar chemical makeup, can also have a significant contribution. We propose that the principle of ion selectivity outlined here may provide a rationale for the differentiation of Na(+)- and H(+)-coupled systems in other families of membrane transporters and enzymes

High-resolution structure of the rotor ring of a proton-dependent ATP synthase

The crystal structure of the c-ring from the proton-coupled F1Fo ATP synthase from Spirulina platensis is shown at 2.1-Å resolution. The ring includes 15 membrane-embedded c subunits forming an hourglass-shaped assembly. The structure demonstrates that proton translocation across the membrane entails protonation of a conserved glutamate located near the membrane center in the c subunit outer helix. The proton is locked in this site by a precise hydrogen bond network reminiscent of that in Na+-dependent ATP synthases. However, the structure suggests that the different coordination chemistry of the bound proton and the smaller curvature of the outer helix drastically enhance the selectivity of the H+ site against other cations, including H3O+. We propose a model for proton translocation whereby the c subunits remain in this proton-locked state when facing the membrane lipid. Proton exchange would occur in a more hydrophilic and electrostatically distinct environment upon contact with the a subunit interface