Biology subjects

Cho, S.-H.

Publications and source records attributed to Cho, S.-H..

10 recordsLinked to original sources

bioRxiv2026

Microbes on the Mind: Multi-modal Neuroimaging Reveals Gut-Brain Axes in Infants

The gut microbiome develops from birth and is associated with cognition and mental health, but its relationship with early brain maturation remains unclear. We studied 223 typically developing infants aged 0-3 years using multimodal MRI and paired fecal shotgun metagenomics. Microbiome-wide association analysis linked microbial features to cortical morphology, white-matter microstructure, and functional networks. Regularized canonical correlation analysis identified structural-metabolic and functional-taxonomic covariance patterns. Sparse partial least-squares analysis recapitulated both full-sample CCA patterns and their defining structural and functional phenotypes, providing cross-method corroboration. Longitudinal canonical-score slopes did not significantly covary, whereas earlier neuroimaging CCA1 scores predicted microbiome CCA1 scores 1-6 months later in bidirectional autoregressive cross-lag models. These observational results identify coordinated developmental patterns and temporal ordering without establishing causality.

developmental biology↗

bioRxiv2026

Stress-induced Membrane Insertion at the β-Barrel Assembly Machinery Complex Regulates BepA Metalloprotease Activity

Proteases must be tightly regulated to prevent uncontrolled degradation, yet the mechanisms ensuring such control remain poorly understood. Members of the widespread M48 metalloprotease family are kept inactive by an autoinhibitory plug that blocks catalytic water activation, but how this plug is released was unknown. Here, using genetic, biochemical and cryo-EM approaches, we discover the activation mechanism of BepA, a quality-control protease that preserves outer membrane integrity by surveilling the {beta}-barrel assembly machinery (BAM) in Gram-negative bacteria. Our cryo-EM analysis of BepA engaged with a stalled BAM-substrate assembly complex revealed that a flexible, unstructured 6-lid covering the active site in the latent protein functions as a molecular harpoon, inserting into the outer membrane when a substrate stalls at BAM and thereby docking BepA at the complex. This membrane anchoring promotes displacement of the autoinhibitory plug and unlocks protease activity precisely where and when it is needed. Thus, a dual enzyme activation mechanism is coupled to membrane association under stress, ensuring that BepA remains inactive until properly localized. Our findings reveal how membranes themselves can license protease activation, a principle that may extend beyond M48 metalloproteases.

microbiology↗

bioRxiv2026

The chitin receptor-interacting protein LIK1 regulates extracellular ATP signaling via interaction with P2K1 in Arabidopsis thaliana

Previously, the chitin receptor-interacting protein kinase LIK1 (LysM receptor kinase 1/CERK1-interacting kinase) was shown to play an important role in regulating chitin signaling and plant defense. A limited proteolysis proteomics study revealed several LIK1-derived peptides that showed differential abundance between ATP-treated and mock-treated Arabidopsis samples, suggesting a possible involvement of LIK1 in extracellular ATP (eATP) signaling. To explore this possibility, LIK1 mutants were obtained and examined for their response to ATP. The results showed that mutations in LIK1 significantly reduced the expression of eATP-responsive genes. In addition, LIK1 was found to interact with the eATP receptor P2K1 and to be phosphorylated by it. The LIK1 protein was localized to the plasma membrane and its gene expression appeared to be ubiquitous. Collectively, these findings indicate that LIK1 not only contributes to chitin signaling but also participates in eATP signaling, highlighting its potential role as a shared component in multiple signaling pathways to regulate plant responses to diverse internal and external cues.

plant biology↗

bioRxiv2025

Fine-tuning of outer membrane-peptidoglycan tethering by the redox-active lipoprotein LppB from Salmonella enterica

The bacterial envelope is an essential compartment for survival, acting as a protective and permeability barrier. In diderm bacteria, it comprises an inner membrane, a thin peptidoglycan layer, and an outer membrane. A stable outer membrane-peptidoglycan connection is crucial for envelope integrity, preventing outer membrane detachment and enabling the generation of periplasmic turgor that counterbalances cytoplasmic pressure, thereby limiting susceptibility to antibiotics and environmental stressors. In Escherichia coli, the major lipoprotein Lpp (Brauns lipoprotein) serves as the only covalent linker between the outer membrane and peptidoglycan, through its unique C-terminal lysine residue. Homologs of Lpp are widely conserved among Enterobacteriaceae, including Salmonella enterica serovar Typhimurium, which encodes LppA and LppB. While Lpp and LppA function similarly, the role of LppB remains unclear. Using E. coli as a surrogate model, we investigated the structural and functional properties of Salmonella LppB. Here, we demonstrate that LppB forms disulfide-linked dimers via its unique C-terminal cysteine and crosslinks to peptidoglycan through its terminal lysine, albeit with significantly lower efficiency than Lpp. Notably, LppB interacts with Lpp to form heterotrimers, thereby reducing overall Lpp-peptidoglycan crosslinking. These findings suggest that LppB modulates outer membrane-peptidoglycan tethering by fine-tuning the bacterial envelope architecture in response to environmental conditions. Given the established link between outer membrane-peptidoglycan uncoupling and outer membrane vesicles (OMV) formation, a key mechanism in bacterial pathogenicity, our results suggest a model in which LppB regulates outer membrane-peptidoglycan attachment, potentially influencing OMV production. This study highlights a modulating role for LppB in envelope remodeling, providing new insights into how Salmonella adapts its envelope structure in response to environmental cues to enhance fitness and virulence.

microbiology↗

bioRxiv2023

Soybean RIN4 represents a mechanistic link between plant immune and symbiotic signaling

The legume-rhizobium symbiosis represents a unique and beneficial interaction between legumes and nitrogen-fixing soil bacteria, called rhizobia. The initiation and development of this symbiosis is complex and begins with recognition of key molecular signals, produced by the plant and its symbiont, which determine symbiotic compatibility. Current data suggest that the invading symbiont initially triggers plant immune responses that are subsequently suppressed. Hence, there is growing evidence that features of plant immunity may be relevant to symbiotic establishment. RIN4 is a key immune regulator in plants, regulating basal immunity and it is also targeted by pathogen effector proteins that either confer susceptibility or resistance, depending on the presence of the appropriate resistance protein. Surprisingly, we found that RIN4 was rapidly phosphorylated upon rhizobial inoculation of soybean root hairs. RNAi silencing and mutant studies indicate that RIN4 expression is essential for effective nodulation of soybean. RIN4 phosphorylation occurs within a fifteen amino acid motif, which is highly conserved within the Fabales (legumes) and Rosales orders, which comprise species capable of nitrogen-fixing endosymbiosis with rhizobia. RIN4 proteins mutated in this conserved phosphorylation site failed to support efficient soybean nodulation. Phosphorylation of this site is mediated by the symbiotic receptor-like kinase, SymRK, a well-studied member of the symbiotic signaling pathway. The data implicate RIN4 phosphorylation as a key mediator of rhizobial compatibility, interconnecting symbiotic and immune signaling pathways. SignificanceThe nitrogen fixing legume-rhizobium symbiosis is a cornerstone of sustainable agriculture, with ongoing efforts to transfer this unique ability to non-leguminous crop plants. Plants are surrounded by a myriad of microbes in the soil, and, therefore, require constant surveillance in order to distinguish between a pathogen or symbiont. Plants monitor for specific molecular signals that indicate pathogen or symbiont presence. We show that RIN4, a key immune regulator, plays an essential role in promoting the development of the symbiotic nitrogen-fixing relationship between soybean and its compatible symbiont Bradyrhizobium japonicum. Therefore, RIN4 is likely a key player in mediating the appropriate response upon infection by friend or foe.

plant biology↗

bioRxiv2023

The outer membrane and peptidoglycan layer form a single mechanical device balancing turgor

Bacteria are subject to a substantial concentration differential of osmolytes between the interior and exterior of the cell, which results in cytoplasmic turgor pressure. Failure to mechanically balance turgor pressure causes cells to burst. Here, we show that in Gram-negative bacteria, the outer membrane and peptidoglycan layer function together to resist turgor: when attached to each other, these two layers form a robust mechanical unit that allows pressure build-up in the periplasmic compartment, which in turn balances cytoplasmic turgor across the inner membrane, preventing cell death. Thus, the peptidoglycan layer is necessary but not sufficient to maintain turgor, which challenges the general view that protecting cells from bursting is the specific task of the peptidoglycan cell wall. ONE-SENTENCE SUMMARYThe peptidoglycan and outer membrane are interconnected layers that cooperate to balance cytoplasmic turgor.

microbiology↗

bioRxiv2023

Conservation implications of elucidating the Korean wolf taxonomic ambiguity through whole-genome sequencing

The taxonomic status of the now likely extirpated Korean Peninsula wolf has been extensively debated, with some arguing it represents an independent wolf lineage, Canis coreanus. To investigate the Korean wolf genetic affiliations and their taxonomic implications, we sequenced and analysed the genomes of a historical Korean wolf dated to the beginning of the 20th century, and a captive wolf originally located at the Pyongyang Central Zoo. Our results indicated that the Korean wolf bears similar genetic ancestry to other regional East Asian populations, therefore suggesting it is not a distinct taxonomic lineage. We identified regional patterns of wolf population structure and admixture in East Asia with potential conservation consequences in the Korean Peninsula and on a regional scale. We find the Korean wolf has similar diversity and inbreeding to other East Asian wolves. Finally, we show that, in contrast to the historical sample, the captive wolf is more genetically similar to wolves from the Tibetan Plateau, hence, Korean wolf conservation programs might not benefit from the inclusion of this specimen.

evolutionary biology↗

bioRxiv2021

Disorder is a critical component of lipoprotein sorting in Gram-negative bacteria

Gram-negative bacteria express structurally diverse lipoproteins in their envelope. Here we found that approximately half of lipoproteins destined to the Escherichia coli outer membrane display an intrinsically disordered linker at their N-terminus. Intrinsically disordered regions are common in proteins, but establishing their importance in vivo has remained challenging. Here, as we sought to unravel how lipoproteins mature, we discovered that unstructured linkers are required for optimal trafficking by the Lol lipoprotein sorting system: linker deletion re-routes three unrelated lipoproteins to the inner membrane. Focusing on the stress sensor RcsF, we found that replacing the linker with an artificial peptide restored normal outer membrane targeting only when the peptide was of similar length and disordered. Overall, this study reveals the role played by intrinsic disorder in lipoprotein sorting, providing mechanistic insight into the biogenesis of these proteins and suggesting that evolution can select for intrinsic disorder that supports protein function.

biochemistry↗

bioRxiv2020

Defining the function of OmpA in the Rcs stress response

OmpA, a protein commonly found in the outer membrane of Gram-negative bacteria, has served as a paradigm for the study of {beta}-barrel proteins for several decades. In Escherichia coli, OmpA was previously reported to form complexes with RcsF, a surface-exposed lipoprotein that triggers the Rcs stress response when damage occurs in the outer membrane and the peptidoglycan. How OmpA interacts with RcsF and whether this interaction allows RcsF to reach the surface has remained unclear. Here, we integrated in vivo and in vitro approaches to establish that RcsF interacts with the C-terminal, periplasmic domain of OmpA, not with the N-terminal {beta}-barrel, thus implying that RcsF does not reach the bacterial surface via OmpA. Our results reveal a novel function for OmpA in the cell envelope: OmpA competes with the inner membrane protein IgaA, the downstream Rcs component, for RcsF binding across the periplasm, thereby regulating the Rcs response.

microbiology↗

bioRxiv2019

Structural insight into the formation of lipoprotein-β-barrel complexes by the β-barrel assembly machinery

The {beta}-barrel assembly machinery (BAM) inserts outer membrane {beta}-barrel proteins (OMPs) in the outer membrane of Gram-negative bacteria. In Enterobacteriacea, BAM also mediates export of the stress sensor lipoprotein RcsF to the cell surface by assembling RcsF-OMP complexes. Although BAM has been the focus of intense research due to its essential activity in generating and maintaining the outer membrane, how it functions remains poorly understood. Here, we report the crystal structure of the key BAM component BamA in complex with RcsF. BamA adopts an inward-open conformation, with the lateral gate to the membrane closed. The globular domain of RcsF is lodged deep inside the lumen of the BamA barrel, binding regions proposed to undergo an outward and lateral opening during OMP insertion. Our structural and biochemical data indicate a push-and-pull mechanism for RcsF export upon conformational cycling of BamA and provide a mechanistic explanation for how RcsF uses its interaction with BamA to detect envelope stress. Our data also suggest that the flux of incoming OMP substrates is involved in the control of BAM activity. Overall, the structural insights gleaned here elucidate a fundamental biological process and suggest a new avenue for antibiotic development.

microbiology↗