Biology subjects

Petersen, H. A.

Publications and source records attributed to Petersen, H. A..

3 recordsLinked to original sources

bioRxiv2026

O-GlcNAc transferase regulates H2O2 production via p38 MAPK

i.Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by augmented transforming growth factor-{beta} (TGF-{beta}) signaling leading to excessive extracellular matrix (ECM) deposition. The fibroblast-to-myofibroblast-transition (FMT) and metabolic reprogramming of lung fibroblasts (HLFs) are essential to IPF pathogenesis, yet the connection between nutrient metabolism and fibrogenesis remains poorly defined. The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is a nutrient-sensitive enzyme that adds O-GlcNAc moieties to substrates. We previously showed that loss of OGT reverses bleomycin-induced pulmonary fibrosis in mice. Here, using unbiased kinomics, we show that pharmacologic inhibition of OGT suppressed non-canonical TGF-{beta}-induced mitogen-activated protein kinase (MAPK) signaling. Molecular confirmation revealed that TGF-{beta}-induced phosphorylation of p38, but not ERK or JNK, was reduced by OGT blockade. Furthermore, p38 itself was O-GlcNAc-modified, which enhanced its phosphorylation and promoted downstream phosphorylation of the NADPH oxidase subunit, p47phox. Inhibition of OGT, p38, or p47phox reduced reactive oxygen species (ROS) in HLFs, revealing a previously unknown role of OGT-p38-p47phox signaling in ROS production. Collectively, this work establishes that O-GlcNAc-modified p38 enhances p47phox-dependent H2O2 production. HighlightsO_LIUsing PamChip STK arrays, we show that OGT inhibition causes broad kinomic remodeling, including suppression of non-canonical TGF-{beta} MAPKs and multiple CDKs. C_LIO_LIOGT blockade selectively attenuates p38 phosphorylation, despite TGF-{beta}-induced substrate redundancy with ERK and JNK. C_LIO_LIWe provide evidence that p38 MAPK undergoes O-GlcNAcylation in human lung fibroblasts, a modification not previously reported. C_LIO_LIThe study identifies a new signaling axis where O-GlcNAc modification of p38 modulates the phosphorylation of p47phox, therefore regulating NOX-dependent H2O2 production. C_LIO_LIBlocking OGT or inhibiting p38/p47phox dramatically reduces TGF-{beta}-driven H2O2 production in human lung fibroblasts. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/728188v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@114210eorg.highwire.dtl.DTLVardef@8647b8org.highwire.dtl.DTLVardef@1ce814corg.highwire.dtl.DTLVardef@8addec_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

A Bundled Antiparallel Cytochrome Nanowire Structure Suggests Roles in Cell-Cell Electron Transfer and Biofilm Formation

Long-range extracellular electron transfer enables respiring microbes to use minerals, other organisms, or electrodes as electron acceptors by transporting electrons microns away from the cell surface. This process is primarily studied in Geobacter sulfurreducens, which produces at least three different micrometer-long, multi-heme cytochrome nanowires capable of electron transfer. However, the distribution and higher-order structure of these types of cytochrome nanowires remains largely unknown. Here, we employed cryo-electron microscopy to determine the atomic structure of a unique cytochrome nanowire from Desulfuromonas soudanensis WTL, a halophilic, iron- and electrode-reducing bacterium found in deep subsurface brine. These filaments are based on a homolog of the OmcE tetraheme cytochrome, which then assemble into highly ordered bundles of antiparallel filaments. This arrangement likely arises from the association of nanowires extending from adjacent cells. Furthermore, a similar cytochrome bundle structure was observed in Geobacter metallireducens, suggesting that this quaternary structure may be a common feature among nanowires secreted by electroactive microbes. Our findings demonstrate that cytochrome nanowires in diverse taxa can form specialized bundle interfaces, potentially facilitating conductive biofilm formation and representing a novel strategy for microbial electron exchange. More broadly, this work expands understanding of electron transfer mechanisms and demonstrates the production of multi-heme filaments across distinct lineages. These insights could guide future research into cytochrome nanowire secretion and conductive biofilm engineering, with potential applications in electrochemical technologies.

microbiology↗

bioRxiv2024

Structural diversity and clustering of bacterial flagellar outer domains

Supercoiled flagellar filaments function as mechanical propellers within the bacterial flagellum complex, playing a crucial role in motility. Flagellin, the building block of the filament, features a conserved inner D0/D1 core domain across different bacterial species. In contrast, approximately half of the flagellins possess additional, highly divergent outer domain(s), suggesting varied functional potential. In this study, we elucidate atomic structures of flagellar filaments from three distinct bacterial species: Cupriavidus gilardii, Stenotrophomonas maltophilia, and Geovibrio thiophilus. Our findings reveal that the flagella from the facultative anaerobic G. thiophilus possesses a significantly more negatively charged surface, potentially enabling adhesion to positively charged minerals. Furthermore, we analyzed all AlphaFold predicted structures for annotated bacterial flagellins, categorizing the flagellin outer domains into 682 structural clusters. This classification provides insights into the prevalence and experimental verification of these outer domains. Remarkably, two of the flagellar structures reported herein belong to a previously unexplored cluster, indicating new opportunities on the study of the functional diversity of flagellar outer domains. Our findings underscore the complexity of bacterial flagellins and open up possibilities for future studies into their varied roles beyond motility.

microbiology↗