Biology subjects

Wang, Z.-X.

Publications and source records attributed to Wang, Z.-X..

8 recordsLinked to original sources

bioRxiv2026

A retinal adrenergic module tunes mammalian visual evolution

How conserved neural circuits are modified during mammalian evolution remains poorly understood. Here we combine cross-species single-cell transcriptomics, in situ validation, retinal physiology, and conditional genetics to identify a superorder-associated adrenergic module in the mammalian retina. We find that ADRB1, which encodes the {beta}1-adrenergic receptor, is uniquely expressed in rod bipolar cells of sampled Euarchontoglires, but is absent from homologous cells in sampled Laurasiatheria and Marsupialia. In mice, {beta}1-adrenergic receptor localizes to rod bipolar cell terminals and boosts transmission to AII amacrine cells through Gs-adenylyl cyclase-cAMP-PKA signaling pathway. This modulation enhances synchronous release, accelerates downstream ganglion cell output, and increases scotopic electroretinographic responses, while rod-bipolar-cell-specific Adrb1 deletion abolishes norepinephrine-induced enhancement without disrupting baseline vision. In the diurnal tree shrew, a Euarchontoglires species with a cone-dominated retina, ADRB1 is instead redeployed from rod bipolar cells to cone photoreceptors. These findings reveal an evolutionarily mobile neuromodulatory module that tunes retinal computation according to visual ecology.

evolutionary biology↗

bioRxiv2024

Telomere-to-telomere genome assembly of a male goat reveals novel variants associated with cashmere traits

A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing novel insights into domestication and selection in goats and related species. Here, we assembled a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), which included a Y chromosome of 20.9 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrected numerous genome-wide structural and base errors in previous assemblies and added 288.5 Mb of previously unresolved regions (PURs) and 446 newly assembled genes to the reference genome. We sequenced the genomes of five representative goat breeds for PacBio reads, and used T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 SVs (7.41%) in the PURs and 507 overlapping genes significantly enriched (Padj. < 0.05) in the keratin filament pathway. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the PURs. Also, our analyses revealed a set of novel selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP).

genomics↗

bioRxiv2023

Filamentation and inhibition of prokaryotic CTP synthase

CTP synthase (CTPS) plays a pivotal role in the de novo synthesis of CTP, a fundamental building block for RNA and DNA, which is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: ATP, UTP, CTP, and GTP. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by virus or prokaryotic pathogens. Utilizing cryo-electron microscopy, we have determined the structure of Escherichia coli CTPS (ecCTPS) filament in complex with CTP, NADH, and the covalent inhibitor DON, achieving a resolution of 2.8[A]. We construct a phylogenetic tree based on differences in filament-forming interfaces and design a variant to validate our hypothesis, providing an evolutionary perspective on the CTPS filament formation. Our computational analysis reveals a solvent-accessible ammonia tunnel upon DON binding. By comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS, differing from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determine and validate the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

biochemistry↗

bioRxiv2023

Structural basis for activation of glutaminase

Glutaminase is a rate-limiting enzyme in glutaminolysis, which produces glutamate from glutamine and enters the TCA cycle[1]. In addition, it plays a key role in redox homeostasis[2], autophagy[3], immune system regulation[4], central nervous system maintenance[5], and senolysis[6]. Therefore, the allosteric regulation of glutaminase is a fascinating topic that has broad implications for our understanding of glutamine metabolism and related diseases[7-9]. Phosphate was discovered as a natural agonist for glutaminase in 1947[10], but the structural basis and mechanism for this regulation remains unclear. Using cryo-electron microscopy, here we determine the structure of human glutaminase with phosphate. This structure allows us to capture phosphate binding at the dimer-dimer interface at near atomic resolution, revealing an allosteric activation mechanism by remodelling the catalytic pocket. Surprisingly, we find that phosphate antagonizes BPTES (a classical antagonist) and CB-839 (the current subject of several phase II clinical trials). Accurate identification of phosphate binding sites lays the foundation for the design of glutaminase agonists and antagonists with broad pharmaceutical significance.

biochemistry↗

bioRxiv2021

Recurrent de novo single point mutation on the gene encoding Na+ /K+ pump results in epilepsy

The etiology of epilepsy remains undefined in two-thirds of patients. Here, we identified a de novo mutation of ATP1A2 (c.2426 T>G, p.Leu809Arg), which encodes the 2 subunit of Na+/K+-ATPase, from a family with idiopathic epilepsy. This mutation caused seizures in the study patients. We generated the point mutation mouse model Atp1a2L809R, which recapitulated the epilepsy observed in the study patients. In Atp1a2L809R/WT mice, convulsions were observed and cognitive and memory function was impaired. This mutation affected the potassium binding function of the protein, disabling its ion transport ability, thereby increasing the frequency of nerve impulses. Our work revealed that ATP1A2L809R mutations cause a predisposition to epilepsy. Moreover, we first provide a point mutation mouse model for epilepsy research and drug screening.

neuroscience↗

bioRxiv2020

Molecular basis of ubiquitination catalyzed by the bacterial transglutaminase MavC

The Legionella pneumophila effector MavC is a transglutaminase that carries out atypical ubiquitination of the ubiquitin (Ub) E2 conjugation enzyme UBE2N by catalyzing the formation of an isopeptide bond between Gln40 of Ub and Lys92 (or to a less extent, Lys94) of UBE2N, which results in inhibition of UBE2N signaling in the NF-{kappa}B pathway. In the absence of UBE2N, MavC deamidates Ub at Gln40 or catalyzes self-ubiquitination. However, the mechanisms underlying these enzymatic activities of MavC are not fully understood at molecular level. In this study, we obtained the structure of the MavC-UBE2N-Ub ternary complex that represents a snapshot of covalent cross-linking of UBE2N and Ub catalyzed by MavC. The structure reveals the unique way by which the cross-linked catalytic product UBE2N-Ub binds mainly to the Insertion and the Tail domains of MavC prior to its release. Based on our structural, biochemical and mutational analyses, we proposed the catalytic mechanism for both the deamidase and the transglutaminase activities of MavC. Finally, by comparing the structures of MavC and MvcA, the homologous protein that reverses MavC-induced UBE2N ubiquitination, we identified several key regions of the two proteins responsible for their opposite enzymatic activity. Our results provide insights into the mechanisms for substrate recognition and ubiquitination mediated by MavC as well as explanations for the opposite activity of MavC and MvcA.

microbiology↗

bioRxiv2020

Extravagant leaf display in Actinidia kolomikta attracting pollinators and maintaining photosynthetic capacity

Pollinators usually are attracted by flower displays, but whether non-green leaves display can function as a flower guide is less well studied. Furthermore, it is still largely unknown whether photosynthetic cost is paid-off by benefits afforded by attraction pollinators and how non-green leaves maintain photosynthetic capacity. Thus, white leaf and inflorescence/flower traits, pollinator visitation, fruit set and seed production, spectral properties, leaf structure, net photosynthetic rate and chlorophyll fluorescence of adaxial and abaxial surface were studied in Actinidia kolomikta (Rupr. & Maxim.) Maxim. The reproductive branches of A. kolomikta have a large number of white leaves at the exterior canopy, but white inflorescences grow at the canopys interior, and we found that showy display of white leaves attracted pollinators reach the flowers. Although incident light was reflected largely, we found that photosynthetic rate of white leaves was maintained at relatively high levels. Furtherly, spongy tissue play the vital role in maintenance photosynthetic capacity of white leaves, which effectively supports inflorescence development during flowering. Thus, white leaves of A. kolomikta enhanced reproductive fitness through attracting pollinators and decreasing reproductive cost: (1) spatially via white leaves locating at reproductive branches and temporally via synchronism between white leaves and flowers; (2) increasing white leaves display and decreasing investment in reproduction; (3) compensatory mechanisms via maintaining photosynthetic capacity of white leaves. Therefore, we propose that these dual functions of white leaves during blossom lower the plants cost of reproduction, and that this is an adaptation to the climatic challenges of the high altitudes and latitudes at which it grows.

plant biology↗

bioRxiv2019

TEsorter: lineage-level classification of transposable elements using conserved protein domains

SummaryTransposable elements (TEs) constitute an import part in eukaryotic genomes, but their classification, especially in the lineage or clade level, is still challenging. For this purpose, we propose TEsorter, which is based on conserved protein domains of TEs. It is easy-to-use, fast with multiprocessing, sensitive and precise to classify TEs especially LTR retrotransposons (LTR-RTs). Its results can also directly reflect phylogenetic relationships and diversities of the classified LTR-RTs.\n\nAvailabilityThe code in Python is freely available at https://github.com/zhangrengang/TEsorter.

bioinformatics↗