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Science China(Life Sciences) 2024年第2期67卷 391-402页

作者： Awei Zhang Haizhen Zhang Ronghua Wang Hongfu He Baoan Song Runjiang Song National Key Laboratory of Green Pesticide Key Laboratory of Green Pesticide and Agricultural BioengineeringMinistry of EducationCenter for R&D of Fine Chemicals of Guizhou UniversityGuiyang 550025China

The prevention and control of rice bacterial leaf blight(BLB)disease has not yet been achieved due to the lack of effective agrochemicals and available targets.Herein,we develop a series of novel bissulfones and a novel target with a unique mechanism to address this challenge.The developed bissulfones can control Xanthomonas oryzae pv.oryzae(Xoo),and 2-(bis(methylsulfonyl)methylene)-N-(4-chlorophenyl)hydrazine-1-carboxamide(B_(7))is more effective than the commercial drugs thiodiazole copper(TC)and bismerthiazol(BT).Pyruvate kinase(PYK)in Xoo has been identified for the first time as the target protein of our bissulfone B_(7).PYK modulates bacterial virulence via a CRP-like protein(Clp)/two-component system regulatory protein(reg R)axis.The elucidation of this pathway facilitates the use of B_(7)to reduce PYK expression at the transcriptional level,block PYK activity at the protein level,and impair the interaction within the PYK-Clp-reg R complex via competitive inhibition,thereby attenuating bacterial biology and pathogenicity.This study offers insights into the molecular and mechanistic aspects underlying anti-Xoo strategies that target PYK.We believe that these valuable discoveries will be used for bacterial disease control in the future.

关键词： 2-bissulfone-N-phenylhydrazine-1-carboxamide derivatives Xoo antibacterial activities pyruvate kinase Regulatory mechanism

Oligomerization of drug transporters:Forms,functions,and mechanisms

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1924-1938页

作者： Chunxu Ni Mei Hong College of Life Sciences South China Agricultural UniversityGuangzhou 510642China Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms South China Agricultural UniversityGuangzhou 510642China

Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance.With our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the Regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic efficacy.In this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the Regulatory mechanisms of oligomerization.Finally,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.

关键词： Drug development Drug transporters Oligomerization Protein expression Protein–protein interaction Regulatory mechanism Structural basis Transport function

regulatory dynamics of the higher-plant PSI-LHCI supercomplex during state transitions

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Molecular Plant 2023年第12期16卷 1937-1950页

作者： Jianghao Wu Shuaijiabin Chen Chao Wang Weijun Lin Chao Huang Chengxu Fan Dexian Han Dandan Lu Xiumei Xu SenFang Sui Lixin Zhang State Key Laboratory of Crop Stress Adaptation and Improvement School of Life SciencesHenan UniversityJinming AvenueKaifeng 475004China School of Life Science Southern University of Science and TechnologyShenzhen 518055China State Key Laboratory of Membrane Biology Beijing Advanced Innovation Center for Structural BiologyBeijing Frontier Research Center for Biological StructureSchool of Life SciencesTsinghua UniversityBeijing 100084China Cryo-EM Center Southern University of Science and TechnologyShenzhen 518055China Photosynthesis Research Center Key Laboratory of PhotobiologyInsttute of BotanyChinese Academy of SciencesBejing 100093China

State transition is a fundamental light acclimation mechanism of photosynthetic organisms in response to the environmental light conditions.This process rebalances the excitation energy between photosystemI(PSl)and photosystem Il through regulated reversible binding of the light-harvesting complex Il(LHCll)to PSl.However,the structural reorganization of PSI-LHCI,the dynamic binding of LHCll,and the Regulatory mechanisms underlying state transitions are less understood in higher plants.In this study,using cryoelectron microscopy we resolved the structures of PSI-LHCI in both state 1(PSI-LHCI-ST1)and state 2(PSILHCI-LHCll-ST2)from Arabidopsis thaliana.Combined genetic and functional analyses revealed novel contacts between Lhcb1 and PsaK that further enhanced the binding of the LHCll trimer to the PSI core with the known interactions between phosphorylated Lhcb2 and the PsaL/PsaH/PsaO subunits.Specifically,PsaO was absent in the PSI-LHCI-ST1 supercomplex but present in the PSI-LHCI-LHCIl-ST2 supercomplex,in which the PsaL/PsaK/PsaA subunits undergo several conformational changes to strengthen the binding of PsaO in ST2.Furthermore,the PSI-LHCI module adopts a more compact configuration with shorter Mg-to-Mg distances between the chlorophylls,which may enhance the energy transfer efficiency from the peripheral antenna to the PSl core in ST2.Collectively,our work provides novel structural and functional insights into the mechanisms of light acclimation during state transitions in higher plants.

关键词： state transitions dynamic conformation photosystem l Regulatory mechanism Arabidopsis thaliana

Molecular regulatory events of flower and fruit abscission in horticultural plants

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Horticultural Plant Journal 2023年第5期9卷 867-883页

作者： Yuan Shi Bangqian Song Qin Liang Deding Su Wang Lu Yudong Liu Zhengguo Li Key Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China Center of Plant Functional Genomics Institute of Advanced Interdisciplinary StudiesChongqing UniversityChongqing 401331China

Flower and fruit abscission is a highly programmed physiological process,which is closely related to the yield of horticultural plants.The coordination of many regulatory factors associated with metabolic and signaling pathways plays a key role in the flower and fruit shedding.Hormones,peptides,carbohydrates,polyamines or cell wall modifying proteins regulate flower and fruit shedding.This article reviewed the recent studies of flower and fruit abscission,including the molecular regulation mechanism of abscission zone formation,typical structure and location of abscission zones,and other factors affecting flower and fruit abscission,such as stresses,hormones,peptides,carbohydrates,polyamines and cell wall modifying proteins.Overall,the review summarizes the developmental mechanism and the diversity of abscission zones,and the key factors affecting flower and fruit abscission of horticultural plants,aiming to provide guidance for studying the molecular Regulatory mechanism of flower and fruit abscission.

关键词： Horticultural plants Organ abscission Abscission zones(AZs) Regulatory mechanism Flower Fruit

Shining in the dark:the big world of small peptides in plants

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aBIOTECH 2023年第3期4卷 238-256页

作者： Yan-Zhao Feng Qing-Feng Zhu Jiao Xue Pei Chen Yang Yu Guangdong Key Laboratory of Crop Germplasm Resources Preservation and Utilization Key Laboratory of South China Modern Biological Seed IndustryMinistry of Agriculture and Rural AffairsAgro-Biological Gene Research CenterGuangdong Academy of Agricultural SciencesGuangzhou 510640China

Small peptides represent a subset of dark matter in plant proteomes.Through differential expression patterns and modes of action,small peptides act as important regulators of plant growth and development.Over the past 20 years,many small peptides have been identified due to technical advances in genome sequencing,bioinformatics,and chemical biology.In this article,we summarize the classifi-cation of plant small peptides and experimental strategies used to identify them as well as their potential use in agronomic breeding.We review the biological functions and molecular mechanisms of small peptides in plants,discuss current problems in small peptide research and highlight future research directions in this field.Our review provides crucial insight into small peptides in plants and will contribute to a better understanding of their potential roles in biotechnology and agriculture.

关键词： Small peptide Biological function Regulatory mechanism Crop improvement

Regulation mechanism and pathogenic role of lncRNA plasmacytoma variant translocation 1 (PVT1) in human diseases

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Genes & Diseases 2023年第3期10卷 901-914页

作者： Fang Wu Yiping Zhu Caiping Zhou Weiwei Gui Hong Li Xihua Lin Department of Endocrinology Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310016China Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310016China Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310016China

Plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNA (lncRNA) gene identified as a recurrent breakpoint of Burkitt’s lymphomas. Human PVT1 gene is located on region 8q24.21, a well-known cancer risk region, and encodes at least 26 linear ncRNA isoforms and 26 circular RNA isoforms, as well as 6 microRNAs. Several PVT1 functioning models have been reported recently such as competing endogenous RNA (ceRNA) activity and regulating protein stability of oncogenes, especially MYC oncogene. The promoter of PVT1 gene is a boundary element of tumor-suppressor DNA. CircPVT1 derived from PVT1 gene is also a critical non-coding oncogenic RNA. Although substantial advancements have been made in understanding the roles of PVT1 in cancer recently, the detailed mechanisms underlying its functions remain unclear. Herein, we summarize the recent progressions on the mechanisms underlying PVT1 regulated gene expression at different levels. We also discuss the interaction between lncRNA and protein, RNA and DNA, as well as the potential cancer therapy strategy by targeting these networks.

关键词： Cancer ceRNA CircPVT1 Long non-coding RNAs Micr oRNAs MYC PVT1 Regulatory mechanism

Interleukin 6 and interferon gamma haplotypes are related to cytokine serum levels in dogs in an endemic Leishmania infantum region

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Infectious Diseases of Poverty 2023年第1期12卷 62-70页

作者： LuisÁlvarez Pablo-Jesús Marín-García Pilar Rentero-Garrido Celia Pilar Martinez-Jimenez Lola Llobat Department of Animal Production and Health Public Health and Food Science and TechnologyVeterinary Medicine FacultyFacultad de VeterinariaUniversidad Cardenal Herrera-CEUCEU UniversitiesValenciaSpain Precision Medicine Unit INCLIVA Biomedical Research InstituteValenciaSpain Helmholtz Pioneer Campus(HPC) Helmholtz Zentrum MünchenNeuherbergGermany

Background The Ibizan Hound is a canine breed native to the Mediterranean region,where leishmaniasis is an endemic zoonosis.Several studies indicate a low prevalence of this disease in Ibizan Hound dogs,whereas other canine breeds present a high prevalence.However,the underlying molecular mechanisms still remain unknown.The aim of this work is to analyse the relationship between serum levels of cytokines and the genomic profiles in two canine breeds,Ibizan Hound(resistant canine breed model)and Boxer(susceptible canine breed model).Methods In this study,we analyse the haplotypes of genes encoding cytokines related to immune response of Leishmania infantum infection in twenty-four Boxers and twenty-eight Ibizan Hounds apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions.The haplo.glm extension of haplo.score was used to perform a General Linear Model(GLM)regression to estimate the magnitude of individual haplotype effects within each cytokine.Results Mean levels of interferon gamma(IFN-γ),interleukin 2(IL-2)and IL-18 in Boxer dogs were 0.19±0.05 ng/ml,46.70±4.54 ng/ml,and 36.37±30.59 pg/ml,whereas Ibizan Hound dogs present 0.49±0.05 ng/ml,64.55±4.54 ng/ml,and 492.10±31.18 pg/ml,respectively.The GLM regression shows fifteen haplotypes with statistically significant effect on the cytokine serum levels(P<0.05).The more relevant are IL6-CGAAG and IFNG-GCA haplotypes,which increase and decrease the IL-2,IL-8 and IFN-γserum levels,respectively.Conclusions Haplotypes in the IFNG and IL6 genes have been correlated to serum levels of IFN-γ,IL-2 and IL-18,and a moderate effect has been found on IL8 haplotype correlated to IL-8 and IL-18 serum levels.The results indicate that the resistance to L.infantum infection could be a consequence of certain haplotypes with a high frequency in the Ibizan Hound dog breed,while susceptibility to the disease would be related to other specific haplotypes,with high frequency in Boxer.Future studies are needed to elucidate whether these differences and h

关键词： Cytokine Haplotype Dog Immune response Regulatory mechanism Resistance Susceptibility

Genetic and environmental control of rice tillering

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作物学报:英文版 2023年第5期11卷 1287-1302页

作者： Yuping Yan Chaoqing Ding Guangheng Zhang Jiang Hu Li Zhu Dali Zeng Qian Qian Deyong Ren State Key Laboratory of Rice Biology and Breeding China National Rice Research InstituteHangzhou 310006ZhejiangChina

Increasing tiller number is a target of high-yield rice breeding. Identification of tiller-defect mutants and their corresponding genes is helpful for clarifying the molecular mechanism of rice tillering. Summarizing research progress on the two processes of rice tiller formation, namely the formation and growth of axillary meristem, this paper reviews the effects of genetic factors, endogenous hormones, and exogenous environment on rice tillering, finding that multiple molecular mechanisms and signal pathways regulating rice tillering cooperate rice tillering, and discusses future research objectives and application of its Regulatory mechanism. Elucidation of theis mechanism will be helpful for breeding high-yielding rice cultivars with ideal plant type via molecular design breeding.

关键词： Rice tiller Axillary meristem Tiller bud Genetic and external factors Regulatory mechanism

lncRNAX-inactive-specific transcript is a potential biomarker related to changes in CD4+T cell levels in systemic lupus erythematosus

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Rheumatology & Autoimmunity 2022年第3期2卷 159-174页

作者： Qi Cheng Xin Chen Jieying Xu Mo Chen Peiyu Zhang Huaxiang Wu Yan Du Department of Rheumatology The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Neurology Linping District Hospital of Integrated Traditional Chinese and Western MedicineHangzhouChina

Background:Systemic lupus erythematosus(SLE)is a particularly heterogeneous autoimmune disease.This study was intended to clarify the correlations between X-inactive-specific transcript(XIST)expression and SLE clinical features and the contribution of XIST to SLE pathogenesis at the transcriptome level.Methods:XIST expression in 79 SLE patients,14 rheumatoid arthritis patients,and 23 healthy controls was determined by quantitative polymerase chain reaction.The Benjamini and Hochberg adjusted method and multivariate linear regression were applied to correct p-values and adjust confounding factors,respectively.Bioinformatic methods were used to explore the function and Regulatory mechanism of XIST.Results:XIST was significantly elevated in peripheral blood mononuclear cells and CD4^(+)T cells from SLE patients compared with the levels in healthy controls and had potential diagnostic value for SLE.Notably,XIST expression was positively correlated with the SLE disease activity index and significantly reduced after effective treatment.Moreover,SLE patients with high XIST expression tended to have elevated levels of CD4^(+)T cells,but reduced levels of NK cells.Bioinformatic analyses suggested that XIST may regulate OLFM4 and CEACAM8 expression by acting as a spongy body for miR-20a,miR-92a,miR-106a,and miR-449a.Furthermore,CEACAM8 was significantly upregulated in CD4^(+)T cells from SLE patients and significantly positively correlated with XIST expression.Conclusions:lncRNA XIST,a potential diagnostic and therapeutic biomarker for SLE,is involved in the change of immune cell balance in the peripheral blood of SLE patients.Mechanistically,XIST may regulate the miR-17-92-CEACAM8 axis to achieve this in CD4^(+)T cells.

关键词： biomarker Regulatory mechanism systemic lupus erythematosus transcriptome XIST

Production of L-glutamate family amino acids in Corynebacterium glutamicum:Physiological mechanism,genetic modulation,and prospects

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Synthetic and Systems Biotechnology 2021年第4期6卷 302-325页

作者： Qi Sheng Xiao-Yu Wu Xinyi Xu Xiaoming Tan Zhimin Li Bin Zhang Jiangxi Engineering Laboratory for the Development and Utilization of Agricultural Microbial Resources College of Bioscience and BioengineeringJiangxi Agricultural UniversityNanchang330045China State Key Laboratory of Biocatalysis and Enzyme Engineering School of Life SciencesHubei UniversityWuhan430062China

L-glutamate family amino acids(GFAAs),consisting of L-glutamate,L-arginine,L-citrulline,L-ornithine,L-proline,L-hydroxyproline,γ-aminobutyric acid,and 5-aminolevulinic acid,are widely applied in the food,pharmaceutical,cosmetic,and animal feed industries,accounting for billions of dollars of market activity.These GFAAs have many functions,including being protein constituents,maintaining the urea cycle,and providing precursors for the biosynthesis of pharmaceuticals.Currently,the production of GFAAs mainly depends on microbial fermentation using Corynebacterium glutamicum(including its related subspecies Corynebacterium crenatum),which is substantially engineered through multistep metabolic engineering strategies.This review systematically summarizes recent advances in the metabolic pathways,Regulatory mechanisms,and metabolic engineering strategies for GFAA accumulation in C.glutamicum and C.crenatum,which provides insights into the recent progress in L-glutamate-derived chemical production.

关键词： L-glutamate family Amino acids C.glutamicum Regulatory mechanism Metabolic engineering Fermentation