Biology subjects

Sheng, D.

Publications and source records attributed to Sheng, D..

7 recordsLinked to original sources

bioRxiv2026

Spatial specialization of antioxidant defenses dictates predation success in Myxococcus xanthus

Redox-based chemical warfare is a primary driver of microbial community assembly. Here, we show that the predatory bacterium Myxococcus xanthus employs a spatial division of labor between two inducible monofunctional catalases, mxKatB and mxKatE, to overcome prey-derived hydrogen peroxide (H2O2). Quantitative transcript analysis revealed distinct regulatory specificities: mxkatB was the dominant transcriptional responder to exogenous H2O2, whereas mxkatE was preferentially induced by UV irradiation. Biochemical analyses demonstrated strict compartmentalization of enzymatic activity. mxKatE functioned intracellularly, consistent with a role in mitigating endogenous genotoxic stress. In contrast, mxKatB, which harbors an N-terminal Sec-dependent signal peptide, was exclusively localized to the extracellular milieu. Targeted gene deletions corroborated these non-redundant physiological roles. {Delta}katE mutant exhibited severe growth defects and heightened sensitivity to UV and H2O2 yet retained full predation proficiency. Conversely, {Delta}katB mutant displayed unaltered vegetative fitness but were severely impaired in prey lysis due to oxidative inactivation of secreted bacteriolytic enzymes. Failure of cross-complementation confirmed that spatial localization, rather than catalytic capacity, dictates enzyme function. Our findings establish that M. xanthus deploys an extracellular catalase shield to protect its exoenzyme arsenal from prey-derived oxidants. This spatial specialization of antioxidant defenses represents a sophisticated strategy that directly determines the outcome of bacterial predation and shapes interspecies interactions within microbial communities. IMPORTANCEPredatory bacteria such as M. xanthus must withstand chemical defenses deployed by their prey. We show that M. xanthus uses a spatially specialized antioxidant system: an extracellular catalase (mxKatB) secreted to shield its lytic enzymes from prey-derived hydrogen peroxide, and an intracellular catalase (mxKatE) that handles endogenous oxidative stress. This division of labor reveals that bacterial antioxidant defenses can be compartmentalized to protect extracellular weaponry rather than the cell itself, adding a new dimension to how spatial organization of stress responses influences the outcome of microbial competition.

ecology↗

bioRxiv2025

Long-term exposure to microplastics and heat affects bumblebee behavior patterns, colony development and social networks

Pollinators are crucial for terrestrial ecosystems and global food security, but their populations are declining from multiple stressors including pollution and climate change. The effects of plastic pollution alone or in interaction with climate change on pollinators remain largely unexplored. Here, we investigate sublethal microplastic exposure effects on pollinators at individual, colony and network level in combination with heating to simulate climate warming. We conducted a one-generation trial on 30 bumblebee (Bombus terrestris) colonies in a customized beekeeping structure with a nesting and a foraging room, where colonies were maintained under optimal temperature (25 {square}) or heated condition (30 {square}), and fed with oil-seed rape pollens and 50% w/w sucrose solution containing 0, 10, or 100 mg/L 30 m polyethylene beads. Real-time tracking with object detection (F1 = 83%) and matrix code scanning showed that microplastic exposure and heat significantly stimulated individual activity and altered labor division. Workers shifted to nursing behaviors and foraged more frequently for sucrose solution and less for pollen. Brood development was impaired by up to 48%, and colony population growth was restrained by 12-15%. Microplastic exposure and heating also significantly intensified social interactions and increased the dominance of the queen in her colony. These findings suggest that plastic pollution has complex, cross-level impacts on bumblebee colonies and their pollination potential, which may be exacerbated under climate change.

ecology↗

bioRxiv2024

Identification of BiP as a temperature sensor mediating temperature-induced germline sex reversal

Besides regulation by karyotype, sex determination is also modulated by environmental cues like temperature, but the involving temperature-transduction mechanism remains elusive. Moreover, while sex determination was traditionally seen as dictated exclusively by either karyotype or temperature, recent observations suggest these factors can co-regulate sex, posing a mechanistic mystery. Here, we discovered that certain wild-isolated and mutant C. elegans strains displayed genotypic-germline-sex-determination (GGSD) but with a temperature override. We found that ER chaperone BiP transduces temperature into germline-sex-governing signal and enables the co-existence of GGSD and temperature-dependent-germline-sex-determination (TGSD). Mechanistically, BiP availability is reduced at warmer temperatures through detecting increased ER-protein-folding burden, which promotes male-germline-fate through ERAD-mediated downregulation of the oocyte-fate driving factor, TRA-2. Remarkably, we can induce a switch between GGSD and TGSD by manipulating this newly-discovered process. Functionally, TGSD facilitates C. elegans hermaphrodites in maintaining brood size at warmer temperatures. Moreover, BiP also acts in germline-sex-determination in a dioecious nematode. Collectively, our findings identify thermosensitive BiP as a conserved temperature sensor in TGSD and provide mechanistic insights into the fascinating transition of GGSD and TGSD.

developmental biology↗

bioRxiv2023

Structural insights into the orthosteric inhibition of P2X receptors by non-ATP-analog antagonists

P2X receptors are extracellular ATP-gated ion channels that form homo-or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, and play critical roles in physiological processes such as neurotransmission, inflammation, pain, and cancer. As a result, P2X receptors have attracted considerable interest as drug targets, and various competitive inhibitors have been developed. However, although several P2X receptor structures from different subtypes have been reported, the limited structural information of P2X receptors in complex with competitive antagonists hampers the understanding of orthosteric inhibition, hindering the further design and optimization of those antagonists for drug discovery. Here, we determined the cryo-EM structures of the mammalian P2X7 receptor in complex with two classical competitive antagonists of pyridoxal-5-phosphate derivatives, PPNDS and PPADS, at 3.3 and 3.6 [A] resolution, respectively, and performed structure-based mutational analysis by patch-clamp recording as well as MD simulations. Our structures revealed the orthosteric site for PPADS/PPNDS, and structural comparison with the previously reported apo-and ATP-bound structures showed how PPADS/PPNDS binding inhibits the conformational changes associated with channel activation. In addition, structure-based mutational analysis identified key residues involved in the PPNDS sensitivity of P2X1 and P2X3, which are known to have higher affinity for PPADS/PPNDS than other P2X subtypes. Overall, our work provides structural insights into the orthosteric inhibition and subtype specificity of P2X receptors by the classical P2X antagonists, pyridoxal-5-phosphate derivatives, thereby facilitating the rational design of novel competitive antagonists for P2X receptors.

biophysics↗

bioRxiv2023

Eyes on nature: Embedded vision cameras for multidisciplinary biodiversity monitoring

Global environmental challenges require comprehensive data to manage and protect biodiversity. Currently, vision-based biodiversity monitoring efforts are mixed, incomplete, human-dependent, and passive. To tackle these issues, we present a portable, modular, low-power device with embedded vision for biodiversity monitoring. Our camera uses interchangeable lenses to resolve barely visible and remote subjects, as well as customisable algorithms for blob detection, region-of-interest classification, and object detection to identify targets. We showcase our system in six case studies from the ethology, landscape ecology, agronomy, pollination ecology, conservation biology, and phenology disciplines. Using the same devices, we discovered bats feeding on durian tree flowers, monitored flying bats and their insect prey, identified nocturnal insect pests in paddy fields, detected bees visiting rapeseed crop flowers, triggered real-time alerts for waterbirds, and tracked flower phenology over months. We measured classification accuracies between 55% and 96% in our field surveys and used them to standardise observations over highly-resolved time scales. The cameras are amenable to situations where automated vision-based monitoring is required off the grid, in natural and agricultural ecosystems, and in particular for quantifying species interactions. Embedded vision devices such as this will help addressing global biodiversity challenges and facilitate a technology-aided global food systems transformation.

ecology↗

bioRxiv2023

Structural insights into the allosteric inhibition of P2X4 receptors

P2X receptors are ATP-activated cation channels involved in a variety of physiological functions. Among the seven subtypes of P2X receptors, the P2X4 subtype plays important roles in both the immune system and the central nervous system, particularly in neuropathic pain. Therefore, P2X4 receptors are of increasing interest as potential drug targets, and several P2X4 subtype-specific inhibitors have been developed. However, the mechanism of allosteric inhibition of P2X4 receptors remains largely unclear due to the lack of structural information. Here, we report the cryo-EM structures of the zebrafish P2X4 receptor in complex with two P2X4 subtype-specific antagonists, BX430 and BAY-1797. Both antagonists bind to the same allosteric site located at the subunit interface at the top of the extracellular domain. Structure-based mutational analysis by electrophysiology identified the important residues for the allosteric inhibition of both zebrafish and human P2X4 receptors. Interestingly, in the previously reported apo structure, the binding pocket is closed and too narrow to accommodate allosteric modulators. Structural comparison revealed the ligand-dependent structural rearrangement of the binding pocket to stabilize the binding of allosteric modulators, which in turn would prevent the structural changes of the extracellular domain associated with channel activation. Furthermore, comparison with the previously reported P2X structures of other subtypes provided mechanistic insights into subtype-specific allosteric inhibition. Overall, the present work provides structural insights into the allosteric inhibition mechanism of P2X4 receptors, facilitating the design and optimization of specific modulators for P2X4 receptors.

biophysics↗

bioRxiv2021

Structural insights into the ion selectivity of the MgtE channel for Mg2+ over Ca2+

MgtE is a Mg2+-selective ion channel whose orthologs are widely distributed from prokaryotes to eukaryotes, including humans, and play an important role in the maintenance of cellular Mg2+ homeostasis. Previous functional analyses showed that MgtE transports divalent cations with high selectivity for Mg2+ over Ca2+. Whereas the high-resolution structure determination of the MgtE transmembrane (TM) domain in complex with Mg2+ ions revealed a Mg2+ recognition mechanism of MgtE, the previous Ca2+-bound structure of the MgtE TM domain was determined only at moderate resolution (3.2 [A] resolution), which was insufficient to visualize the water molecules coordinated to Ca2+ ions. Thus, the structural basis of the ion selectivity of MgtE for Mg2+ over Ca2+ has remained unclear. Here, we showed that the metal-binding site of the MgtE TM domain binds to Mg2+ [~]500-fold more strongly than Ca2+. We then determined the crystal structure of the MgtE TM domain in complex with Ca2+ ions at a higher resolution (2.5 [A] resolution), allowing us to reveal hexahydrated Ca2+, which is similarly observed in the previously determined Mg2+-bound structure but with extended metal-oxygen bond lengths. Our structural, biochemical, and computational analyses provide mechanistic insights into the ion selectivity of MgtE for Mg2+ over Ca2+.

biophysics↗