Biology subjects

Moe, E.

Publications and source records attributed to Moe, E..

4 recordsLinked to original sources

bioRxiv2026

Evidence for strong interplay between the nucleotide and base excision repair pathways in D. radiodurans

Deinococcus radiodurans harbors a largely classical bacterial DNA repair machinery yet displays exceptional resistance to ultra-violet and ionizing radiation. To investigate whether crosstalk between its DNA repair pathways contributes to this phenotype, we mapped putative interactions between the nucleotide excision repair (NER) and base excision repair (BER) pathways, which together are responsible for the removal of nucleobase lesions. Using a bacterial two-hybrid system, we identified multiple direct interactions between NER and BER proteins, notably involving the two UvrA variants, and validated these interactions in vitro. Furthermore, functional analyses revealed that NER interferes with the BER-mediated removal of oxidized guanines by the Fpg DNA glycosylase, likely through competition for DNA binding and sequestration of Fpg. Finally, UvrB and UvrC were found to further process the Fpg incision product in an ATP-dependent, UvrA1-independent manner. Together, these results demonstrate a multi-level crosstalk between NER and BER in D. radiodurans, which may contribute to its extraordinary DNA repair capacity. To our knowledge, this represents the first evidence of such a complex interplay in bacteria.

biochemistry↗

bioRxiv2026

Thermodynamic rigidity of harmonic brain states relates to general mental ability in juvenile myoclonic epilepsy

Cognitive difficulties are increasingly recognized in juvenile myoclonic epilepsy (JME), but scalable biomarkers linking resting-state brain dynamics to general mental ability remain limited. Here, we combined topological data analysis, graph signal processing, machine learning, inverse Langevin modeling, and biophysical simulations to test whether EEG-derived network dynamics capture individual differences in general mental ability in JME. We studied 54 patients with JME and 45 healthy controls using resting-state high-density EEG and the raw estimated full-scale score derived from the Wechsler Abbreviated Scale of Intelligence (WASI), used here as an index of general mental ability. Subject-specific low-alpha activity was reconstructed with generalized eigendecomposition, and graph-derived features were extracted from the projection of topological and alpha-power signals onto the functional connectome, providing a graph-harmonic description of large-scale brain-state dynamics. In controls, dynamic EEG-derived features significantly predicted general mental ability, whereas the same framework failed in JME. Because prediction in controls was driven mainly by dynamic measures of smoothness (Dirichlet energy), we next examined the temporal organization of alpha-power smoothness using an inverse Langevin framework. Within the patient group, greater thermodynamic rigidity--that is, stronger confinement of fluctuations around preferred network states--was associated with lower general mental ability. Relative to controls, patients also showed lower thermodynamic noise, indicating a reduced tendency to explore alternative network regimes. Biophysical simulations suggested that reduced dendritic arborization can generate rigidity directly, whereas pharmacological stabilization of hyperexcitable circuits can shift the system toward a more rigid, lower-noise regime. Together, these findings suggest that cognition in JME is linked not only to altered resting-state network dynamics but also to stronger confinement of network-state fluctuations, with both intrinsic circuit abnormalities and treatment-related stabilization representing plausible routes to this rigid phenotype.

neuroscience↗

bioRxiv2024

Flavin-containing siderophore-interacting protein of Shewanella putrefaciens DSM 9451 reveals substrate specificity in ferric-siderophore reduction

Shewanella are bacteria widespread in marine and brackish water environments and emergent opportunistic pathogens. Their environmental versatility is highly dependent on the ability to produce an abundance of iron-rich proteins, mainly multiheme c-type cytochromes. Although iron plays a vital role in the ability of Shewanella species to survive in various environments, very few studies exist regarding the strategies by which these bacteria scavenge iron from the environment. Small molecule siderophore-mediated iron transport is a strategy commonly employed for iron acquisition, and it was identified amongst Shewanella spp. over two decades ago. Shewanella species produce hydroxamate-type siderophores and iron removal from these compounds can occur in the cytoplasm via Fe(III)-siderophore reduction mediated by siderophore-interacting proteins (SIPs). The genome of Shewanella putrefaciens DSM 9451 isolated from an infected child contains representatives of the two different cytosolic families of SIPs: the flavin-containing siderophore interacting protein family (SIP) and the iron-sulfur cluster-containing ferric siderophore reductase family (FSR). Here, we report the expression and purification of the flavin-containing (SbSIP) and iron-sulfur cluster-containing (SbFSR) Fe(III)-siderophore reductases of Shewanella putrefaciens DSM 9451. The structural and functional characterization of SbSIP shows distinct features from the highly homologous SIP from Shewanella frigidimarina (SfSIP). These include significant structural differences, different binding affinities for NADH and NADPH, and lower rates of Fe(III)-siderophore reduction, results which consolidate in the putative identification of the binding pocket for these proteins. Overall our work highlights NADH and NADPH specificity and the different Fe(III)- siderophore reduction abilities of the SIP family suggesting a tailoring of these enzymes towards meeting different microbial iron requirements.

biochemistry↗

bioRxiv2023

The structure of a novel ferredoxin: FhuF, a ferric-siderophore reductase from E. coli K-12 with a novel 2Fe-2S cluster coordination

Iron is a vital element for life. However, after the Great Oxidation Event, the bioavailability of this element became limited. To overcome iron shortage and to scavenge this essential nutrient, microorganisms use siderophores, secondary metabolites that have some of the highest affinities for ferric iron. The crucial step of iron release from these compounds to be subsequently integrated into cellular components is mediated by Siderophore-Interacting Proteins (SIPs) or Ferric-siderophore reductases (FSRs). In this work, we report the structure of an FSR for the first time. FhuF from laboratory strain Escherichia coli K-12 is the archetypical FSR, known for its atypical 2Fe-2S cluster with the binding motif C-C-X10-C-X2-C. The 1.9 [A] resolution crystallographic structure of FhuF shows it to be the only 2Fe-2S protein known to date with two consecutive cysteines binding different Fe atoms. This novel coordination provides a rationale for the unusual spectroscopic properties of FhuF. Furthermore, FhuF shows an impressive ability to reduce hydroxamate-type siderophores at very high rates when compared to flavin-based SIPs, but like SIPs it appears to use the redox-Bohr effect to achieve catalytic efficiency. Overall, this work closes the knowledge gap regarding the structural properties of ferric-siderophore reductases and simultaneously opens the door for further understanding of the diverse mechanistic abilities of these proteins in the siderophore recycling pathway.

biochemistry↗