Science China-Life Sciences
·
2025
·
IF 9.5
Gui Tianxiang,Liu Ying,Fu Mingfeng,Wu Han,Su Pan,Feng Xuhui,Zheng Mengmeng,Huang Zixuan,Luo Xudong,Boron Walter F.,Chen Li-Ming
Nicotinamide adenine dinucleotide (NAD) is well known as a coenzyme involved in many redox reactions in cellular energy metabolism, or as a substrate for many NAD + -consuming enzymes, including those that generate the second messenger cyclic ADP-ribose or deacetylate proteins (e.g., histones). The role of NAD in non-catalytic proteins is poorly understood. IRBIT and L-IRBIT (the IRBITs) are two cytosolic proteins that are structurally related to dehydrogenases but lack catalytic activity. Instead, by interacting directly with their targets, the IRBITs modulate the function of numerous proteins with important roles, ranging from Ca 2+ signaling and intracellular pH (pH i ) regulation to DNA metabolism to autophagy. Among the targets of the IRBITs is the Na + -HCO 3 − cotransporter NBCe1-B, which plays a central role in intracellular pH (pH i ) regulation and epithelial electrolyte transport. Here, we demonstrate that NAD modulates NBCe1-B activation by serving as a cofactor of IRBIT or L-IRBIT. Blocking NAD salvage pathway greatly decreases NBCe1-B activation by the IRBITs. Administration of the oxidized form NAD + enhances, whereas the reduced form NADH decreases NBCe1-B activity. Our study represents the first example in which the redox state of NAD, via IRBIT or L-IRBIT, modulates the function of a membrane transport protein. Our findings reveal a new role of NAD and greatly expand our understanding of NAD biology. Because the NAD redox state fluctuates greatly with metabolic status, our work provides insight into how, via the IRBITs, energy metabolism could affect pH i regulation and many other IRBIT-dependent processes.
研究领域:
生物化学
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细胞生物学
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生理学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2014
·
IF 5.825
Lizhen Chen,Haili He,Yongdong Jin
Phospholipid vesicles are ubiquitous cellular organelles that perform vital functions including materials transport and information transmission and have found promising biomedical applications. Although the transmembrane translocation (via nanopores) of phospholipid vesicles, especially small unilamellar phospholipid vesicles (SUVs), is recognized to be very important for these processes and applications, the details and dynamics remain not very clear. Herein, we use single conical glass nanopores as a model platform to systematically investigate the translocation dynamics of SUVs (∼50–60 nm in diameter) through small nanopores with orifice diameters ranging from ∼14 to 72 nm. Dynamic translocation of individual SUVs one by one through the nanopores was clearly observed and was analyzed by the occurrence of periodic oscillation in ionic current blockage signal under a negatively applied voltage. Translocation behaviors of the SUVs, in terms of magnitude and duration of ionic current blockage signal, varied and can be modulated by changing nanopore size, solution pH, vesicle concentration, applied voltage, and inner surface charge properties of the nanopores. The translocation rate of the SUVs through an ∼72 nm nanopore is typically on a time scale of a few seconds (per SUV translocation event) and found nonlinearly proportional to the concentration of the SUVs. Moreover, the electrophoretic force has been verified as a main force to drive the SUVs through the nanopore since there is a nearly linear relationship between the current blockage frequency of SUVs translocation and the applied bias potentials ranging from −0.6 to −1 V. The findings provide fundamental insights into the translocation and interactions of SUVs with nanopores, and the reported nanopore platform may find potential useful bioapplications in single-cell and single-vesicle studies.
研究领域:
生物物理学
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纳米技术
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细胞生物学
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DOI
PubMed
高影响因子
Biomicrofluidics
·
2016
·Vol. 10
·期 6
·
IF 2.708
Li Zhen,Luo Qiaohui,Wu Jianmin
A label-free optical sensor was constructed by integrating electrochemically etched porous silicon (pSi) and supported phospholipid bilayers in a microfluidic chip. The translocation of peptides through the phospholipid bilayers could induce a red shift in effective optical thickness of the pSi layer, which could be monitored by reflective interferometric Fourier transform spectroscopy. By measuring the kinetic data of membrane translocating on the phospholipid bilayers/pSi chip, the relationship between the behavior of membrane-translocating peptides (MTPs) and translocating mechanism was established. With these optical data, MTPs with different action modes on the cell membrane can be correctly discriminated. The bio-functionalized microfluidic sensor will provide a reliable and cost-effective platform to study the transmembrane behavior of peptides, which is of great importance in the MTP screening and peptide function study.
研究领域:
生物传感器
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分析化学
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Jinnan Xuan,Shuxian Hou,Yuqiang Han,Chen Li,Yisi Liu,Zhong Li,Xixia Liu,Guoqiang Yang,Xinxin Liu,Jiantao Wang,Yuting Huang,Jun Wang,Wei Lai
Multidrug-resistant bacterial infections have emerged as a global public health crisis due to antibiotic misuse. In this study, we develop a layer-restacked 3D Ti3C2 nanostructure utilizing ice-templating. This nanostructure exhibits outstanding hydrophilicity, biocompatibility, and stability, as well as enhanced absorption, extinction coefficient, and photothermal conversion efficiency. Additionally, the layer-restacked 3D Ti3C2 nanostructure demonstrates excellent antibacterial activity against MDR Escherichia coli and MDR Staphylococcus aureus irradiated by 808 nm near-infrared light (NIR). Specifically, the mechanism of photothermal action against multidrug-resistant bacteria involves structural damage to the bacterial membranes, leading to the leakage of bacterial contents after layer-restacked 3D Ti3C2 nanostructures adhered under NIR irradiation. The results of transcriptome analysis show that the 3D Ti3C2 nanostructure regulates the membrane transporters and membrane transporter proteins on the bacterial cell membrane as well as the activities of enzymes associated with them, which in turn affect the metabolic processes of organic acids and other organic substances in the bacterial cell. The DNA-binding transcriptional activator EvgA is significantly downregulated, which may play a crucial role in inhibiting the emergence of drug resistance in bacteria when exposed to the layer-restacked 3D Ti3C2 nanostructure. The layer-restacked 3D Ti3C2 nanostructure is an effective photothermal antimicrobial nanostructure against multidrug-resistant bacteria.
研究领域:
材料科学
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微生物学
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医学
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DOI
PubMed
高影响因子
WATER RESEARCH
·
2025
·
IF 12.4
Huajing Zhou,Kun Wang,Liang He,Zilian Liu,Dianchao Kong,Qiang Zhang,Song Jin,Ying Han,Qingqing Guan,Guoping Sheng
Groundwater remediation presents significant challenges, while microbial electrocatalytic remediation is promising but suffers from low efficiency due to low periplasmic electron transfer. Unlike traditional methods, which involve directly improving the conditions for electron transfer, herein, we first developed an electron-enhanced proton motive force (PMF) strategy for effective Cr(VI) removal. The proton is used as a new mutagenic source to mutate microorganisms by coupling with a micro-electric field. Interestingly, the dominant bacterial species of Rhizobium can directly capture protons (H + ) and electrons from the cathode as energy sources, resulting in greater than 97% reduction and immobilization of Cr(VI) in groundwater. Since the increase in the proton concentration gradient across the cytoplasmic membrane is due to the free diffusion of protons through new proton transfer channels, the extracellular electron transfer (EET) process is accelerated significantly, and Cr(VI) can also shuttle inside the cell to be reduced. 13 C isotope tracer technology and genetic volcano maps were used to further monitor the active transmembrane ETC transport pathway. The accumulated H + transfers electrons through reduced coenzymes, such as glycoside hydrolases (GH3, GH13-40, and GH5-15) and beta-galactosidase (CBM43), establishing a new transmembrane transfer pathway in the periplasmic space. In addition, unlike conventional bioremediation techniques, the proton gradient intensifies the motive force (PMF-H + ) to accelerate the synthesis of adenosine triphosphate, which provides energy for the bioremediation of Cr(VI), leading to a high bioelectrocatalytic rate. The new PMF-H + strategy successfully restored Cr(VI)-contaminated groundwater in situ to meet the water quality standard, indicating great potential for groundwater remediation.
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DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Yixi Su,Jiwei Chen,Jingyan Hu,Cheng Qian,Jiahao Ma,Sigurður Brynjolfsson,Weiqi Fu
A major obstacle to exploiting industrial flue gas for microalgae cultivation is the unfavorable acidic environment. We previously identified three upregulated genes in the low-pH-adapted model diatom Phaeodactylum tricornutum : ferredoxin (PtFDX), cation/proton antiporter (PtCPA), and HCO 3 − transporter (PtSCL4-2). Here, we individually overexpressed these genes in P. tricornutum to investigate their respective roles in resisting acidic stress (pH 5.0). The genetic modifications enabled positive growths of transgenic strains under acidic stress that completely inhibited the growth of the wild-type strain. Physiological studies indicated improved photosynthesis and reduced oxidative stress in the transgenic strains. Transcriptomes of the PtCPA- and PtSCL4-2-overexpressing transgenics showed widespread upregulation of various transmembrane transporters, which could help counteract excessive external protons. This work highlights ion/electron carrier genes’ role in enhancing diatom resistance to acidic stress, providing insights into phytoplankton adaptation to ocean acidification and a strategy for biological carbon capture and industrial flue gas CO 2 utilization.
研究领域:
植物学
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遗传学
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环境科学
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生物技术
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DOI
PubMed
高影响因子
BMC Medical Genomics
·
2024
·Vol. 17
·期 1
·1-10
·
IF 2.1
Xu Kuishuai,Zhang Liang,Wang Tianrui,Yu Tengbo,Zhao Xia,Zhang Yingze
Objective There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the “gene profile” of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy. Methods A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups’ DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Results T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways ( p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway. Conclusions Transcriptomics reveals dynamic changes in the“gene profiles”of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.
研究领域:
分子生物学
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基因组学
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糖尿病研究
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肌肉骨骼疾病
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Peng Min,Zhang Chen,Duan Yuan-Yuan,Liu Hai-Bo,Peng Xin-Yuan,Wei Qian,Chen Qi-Ying,Sang Hong,Kong Qing-Tao
Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 μg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.
研究领域:
药理学
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微生物学
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传染病学
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真菌学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Ru Huan,Peigen Xu,Shuang Chen,Yao Dong,Chen Zhang,Dan Lu,Yilan Ouyang,Jiangyun Liu,Zhenyu Xuan,Chunshan Gui
Human organic anion transporting polypeptides (OATPs) 1B1 and 1B3 are two closely related transporters. However, OATP1B1- and 1B3-mediated estrone-3-sulfate (E3S) uptake can be differentially modulated by quercetin-3- O -α-L-arabinopyranosyl(1 → 2)-α-L-rhamnopyranoside (QAR), a compound found in some fruits such as jujube. In this study, we isolated QAR from jujube leaves and investigated the molecular mechanism underlying the activation of OATP1B3-mediated E3S uptake by QAR through functional characterization on a range of chimeric transporters derived from OATP1B3 and molecular modeling. Our findings revealed that the residue Ser545 in transmembrane domain 10 (TM10) is crucial for the activation of OATP1B3 by QAR. Kinetic analyses showed that QAR enhances OATP1B3-mediated E3S uptake at low substrate concentrations due to an increase in substrate binding affinity. Mutational analysis and molecular modeling suggested that amino acid residues with smaller side chains at position 545 are vital for the activation of OATP1B3, as bulkier residues could lead to steric collision with E3S. While QAR stimulates OATP1B3-mediated E3S uptake, it inhibits OATP1B3-mediated estradiol-17β-glucuronide/rosuvastatin uptake, indicating that the effect of QAR on OATP1B3's function is substrate-dependent. In summary, Ser545 within TM10 is essential for the activation of OATP1B3-mediated E3S uptake by QAR.
研究领域:
药理学
·
分子生物学
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膜转运
·
药物代谢
·
天然产物
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DOI
PubMed
高影响因子
MOLECULAR CELL
·
2025
·Vol. 85
·期 17
·3209-3224
·
IF 16.6
Xiaojie Wang,Zhongjian Bai,Ciara Wallis,Huanchen Wang,Yaoyao Han,Ruitao Jin,Mingguang Lei,Tian Yang,Chunfang Gu,Henning Jessen,Stephen Shears,Yadong Sun,Ben Corry,Yixiao Zhang
XPR1 is emerging as the only known inorganic phosphate (Pi) exporter in humans, critical for Pi homeostasis, with its activity stimulated by inositol pyrophosphate InsP8 and regulated by neuronal scaffold protein KIDINS220. Our structural studies reveal that InsP8 specifically activates XPR1 in a stepwise manner, involving profound SYG1/PHO/XPR1 (SPX) domain movements. Each XPR1 subunit functions with four gating states, in which Pi permeates a constriction site via a “knock-kiss-kick” process. By contrast, KIDINS220 delicately stabilizes XPR1 in a closed conformation through multiple mechanisms, one of which involves trapping the XPR1 α1 helix—critical for InsP8 binding—within an interaction hub. InsP8 serves as a key to release KIDINS220’s restraint, reinforcing a “key-to-locks” mechanism to safeguard the stepwise activation. Additionally, our study provides direct structural insights into XPR1-associated neuronal disorders and highlights the evolutionary conservation and divergence among XPR1 orthologs, offering a comprehensive understanding of Pi homeostasis across species.
研究领域:
结构生物学
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细胞信号传导
·
代谢
·
膜转运
·
神经生物学
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产品关联
DOI
PubMed
高影响因子
NATURE STRUCTURAL & MOLECULAR BIOLOGY
·
2025
·
IF 10.1
Lai Qinxuan,Xu Mengzhen,Gao Yongxiang,Yang Zhisen,Sun Linfeng,Liu Xin
Glucose-6-phosphate (G6P) transporters are crucial for glucose metabolism by mediating G6P transport from the cytoplasm to endoplasmic reticulum (ER). However, their transport mechanisms remain poorly understood. Here, we elucidate the structural and functional basis of human solute carrier family 37 member 2 (SLC37A2), a G6P transporter implicated in metabolic regulation and macrophage inflammation. We show that SLC37A2 functions as a uniporter, facilitating G6P transport independent of inorganic phosphate gradients. Structures of SLC37A2 in the apo and G6P-bound states reveal a dimeric architecture. Both the ER luminal-open and cytosolic-open structures are captured, showing the structural dynamics during G6P transport. G6P is coordinated by SLC37A2 through interactions with its phosphate and hydroxyl groups. Furthermore, mapping mutations associated with glycogen storage disease type Ib onto SLC37A2 highlights residues essential for transport activity. Together, this work provides structural insights into G6P transport and establishes a framework for understanding related metabolic disorders.
研究领域:
结构生物学
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代谢学
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膜转运
·
分子生物学
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DOI
PubMed
高影响因子
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