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Mechanism of the Rpn13-induced activation of Uch37

Protein & Cell 2014年第8期5卷 616-630页

作者： Lianying Jiao Songying Ouyang Neil Shaw Gaojie Song Yingang Feng Fengfeng Niu Weicheng Qiu Hongtao Zhu Li-Wei Hung Xiaobing Zuo V. Eleonora Shtykova Ping Zhu Yu-Hui Dong Ruxiang Xu Zhi-Jie Liu National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China iHuman Institute ShanghaiTech University Shanghai 201210 China Shandong Provincial Key Laboratory ofEnergy-Genetics Qingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of Sciences Qingdao 266101 China Physics Division 'Los Alamos National Laboratory Los Alamos NM 87545 USA X-ray Science Division Argonne National Laboratory 9700 South Cass Avenue Argonne IL 60439 USA Institute of Crystallography~ Russian Academy of Sciences 59 Leninsky Pr. 117333 Moscow Russian Federation center for Multi-disciplinary Research Institute of High Energy Physics Chinese Academy of Sciences Beijing 100049China Department of Nerosurgery The Military General Hospital of Beijing PLA Beijing 100700 China

Uch37 is a de-ubiquitinating enzyme that is activated by Rpn13 and involved in the proteasomal degradation of proteins. The full-length Uch37 was shown to exhibit low iso-peptidase activity and is thought to be auto-inhibited. Structural comparisons revealed that within a homo- dimer of Uch37, each of the catalytic domains was blocking the other＇s ubiquitin （Ub）-binding site. This blockage likely prevented Ub from entering the active site of Uch37 and might form the basis of auto-inhibition. To understand the mode of auto-inhibition clearly and shed light on the activation mechanism of Uch37 by Rpn13, we investigated the Uch37-Rpn13 complex using a combi- nation of mutagenesis, biochemical, NMR, and small- angle X-ray scattering （SAXS） techniques. Our results also proved that Uch37 oligomerized in solution and had very low activity against the fluorogenic substrate ubi- quitin-7-amino-4-methylcoumarin （Ub-AMC） of de-ubiq- uitinating enzymes. Uch37AHb＇Hc＇KEKE, a truncation removal of the C-terminal extension region （residues 256- 329） converted oligomeric Uch37 into a monomeric form that exhibited iso-peptidase activity comparable to that of a truncation-containing the Uch37 catalytic domain only. We also demonstrated that Rpn13C （Rpn13 residues 270- 407） could disrupt the oligomerization of Uch37 by sequestering Uch37 and forming a Uch37-Rpn13 com- plex. Uch37 was activated in such a complex, exhibiting 12-fold-higher activity than Uch37 alone. Time-resolved SAXS （TR-SAXS） and FRET experiments supported the proposed mode of auto-inhibition and the activation mechanism of Uch37 by Rpn13. Rpn13 activated Uch37 by forming a 1：1 stoichiometric complex in which the active site of Uch37 was accessible to Ub.

关键词： Uch37-Rpn13 complex de-ubiquitination,SAXS analysis oligomerization iso-peptidase

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The 4th ISGO International Conference on Structural genomics

作者： Ruth Nussinov Basic Research program SAIC Frederick Inc.Center for Cancer Research Nanobiology Program NCI-FrederickFrederick MD 21702 Sackler Inst.Of Molecular MedicineDepartment of Human Genetics and Molecular MedicineSackler School of MedicineTel Aviv UniversityTel Aviv 69978Israel

＜正＞Similar binding sites often imply similar protein-protein interactions and similar functions;however, similar binding sites may also constitute traps for nonfunctional associations. How are similar sites distinguished to prevent misassociations? The BRCT domain from the breast cancer-susceptibility gene product BRCA1 is

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Asthma-associated polymorphisms in 17q12-21 locus modulate methylation and gene expression of GSDMA in naive CD4^+ T cells

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Journal of Genetics and genomics 2020年第3期47卷 171-174页

作者： Anne-Marie Madore Lucile Pain Anne-Marie Boucher-Lafleur Andréanne Morin Jolyane Meloche Marie-Michelle Simon Bing Ge Tony Kwan Warren A.Cheung Tomi Pastinen Catherine Laprise Departement des sciences fondamentales Universite du Quebec a ChicoutimiSaguenayQuebecG7H 2B1Canada Department of Human Genetics McGill UniversityMontrealQuebecH3A 0C7Canada Department of Human Genetics University of ChicagoIL60637USA McGill University and Genome Quebec Innovation Centre MontrealQuebecH3A 0G1Canada center for Pediatric Genomic Medicine Kansas CityMO64108USA Centre intersectoriel en sante durable Universite du Quebec a ChicoutimiSaguenayQuebecG7H 2B1Canada

The 17q12-21 locus harboring ORMDL sphingolipid biosynthesis regulator 3(ORMDL3)and Gasdermin B(GSDMB)genes exhibits one of the most significant and replicated associations with asthma[MIM:600807](Stein et al.,2018).Several studies explored the complex interactions between SNPs,gene expression and epigenetic modifications at this locus,primarily focusing on the levels of expressed ORMDL3 and GSDMB(Stein et al.,2018).Given that DNA methylation and gene expression signals are cell-type specific(Reinius et al.,2012),isolated materials such as lymphocytes from blood and,to a lesser extent,bronchial epithelial cells from biopsies of bronchi or bronchoalveolar lavages have been used in a number of studies to investigate such interactions(Stein et al.,2018).

关键词： FDR T cells Asthma-associated polymorphisms gene expression of GSDMA

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Antibiotic Resistance Genes in the Human-Impacted Environment:A One Health Perspective

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Pedosphere 2019年第3期29卷 273-282页

作者： James M. TIEDJE WANG Fang Celia M. MANAIA Marko VIRTA SHENG Hongjie MA Liping ZHANG Tong Edward TOPP Key Laboratory of Soil Environment and Pollution Remediation Institute of Soil Science Chinese Academy of Sciences Nanjing 210008 (China) center for Microbial Ecology Department of Plant Soil and Microbial Sciences Michigan State University East Lansing MI 48824 (USA) University of Chinese Academy of Sciences Beijing 100049 (China) Universidade Catolica Portuguesa CBQF-Centro de Biotecnologia e Quimica Fina一Laboratorio Associado Escola Superior de Biotecnologia Porto 4200-374 (Portugal) Department of Microbiology University of Helsinki Helsinki 00014 (Finland) Environmental Biotechnology Lab The University of Hong Kong Hong Kong (China) London Research and Development Centre Agriculture and Agri-Food Canada and University of Western Ontario London ON N6G 0J3 (Canada)

Antibiotic resistance and its environmental component are gaining more attention as part of combating the growing healthcare crisis. The One Health framework, promulgated by many global health agencies, recognizes that antimicrobial resistance is a truly inter-domain problem in which human health, animal agriculture, and the environment are the core and interrelated *** prospectus presents the status and issues relevant to the environmental component of antibiotic resistance, namely, the needs for advancing surveillance methodology: the environmental reservoirs and sources of resistance, namely, urban wastewater treatment plants, aquaculture production systems, soil receiving manure and biosolid, and the atmosphere which includes longer range ***, much work has been done describing antibiotic resistance genes in various environments;now quantitative, mechanistic,and hypothesis-driven studies are needed to identify practices that reduce real risks and maintain the effectiveness of our current antibiotics as long as possible. Advanced deployable detection methods for antibiotic resistance in diverse environmental samples are needed in order to provide the surveillance information to identify risks and define barriers that can reduce risks. Also needed are practices that reduce antibiotic use and thereby reduce selection for resistance, as well as practices that limit the dispersal of or destroy antibiotic-resistant bacteria or their resistance genes that are feasible for these varied environmental domains.

关键词： animal agriculture antibiotic-resistant bacteria antimicrobial resistance aquaculture human health One Health framework soil contamination wastewater and sludge

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Functional Analysis of Semi-conserved Transit Peptide Motifs and Mechanistic Implications in Precursor Targeting and Recognition

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Molecular Plant 2016年第9期9卷 1286-1301页

作者： Kristen Holbrook Chitra Subramanian Prakitchai Chotewutmontri L. Evan Reddick Sarah Wright Huixia Zhang Lily Moncrief Barry D. Bruce Department of Biochemistry Cellular and Molecular Biology Graduate Program in Plant Physiology and Genetics Graduate School of Genome Science and Technology Department of Botany Department of BotanyUniversity of Tennessee Knoxville TN 37996 USA Present address: Department of Infectious Disease St. Jude Children's Research Hospital Memphis TN 38105 USA Present address: Institute of Molecular Biology University of Oregon Eugene OR 97403 USA present address: Department of Microbiology University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas TX 75390 USA Present address: Albert R. Mann Library Cornell University Ithaca NY 14850 USA present address: U.S. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring MD 20993 USA

Over 95% of plastid proteins are nuclear-encoded as their precursors containing an N-terminal extension known as the transit peptide （TP）. Although highly variable, TPs direct the precursors through a conserved, posttranslational mechanism involving translocons in the outer （TOC） and inner envelope （TOC）. The organelle import specificity is mediated by one or more components of the Toc complex. However, the high TP diversity creates a paradox on how the sequences can be specifically recognized. An emerging model of TP design is that they contain multiple loosely conserved motifs that are recognized at different steps in the targeting and transport process. bioinformatics has demonstrated that many TPs contain semiconserved physicochemical motifs, termed FGLK. In order to characterize FGLK motifs in TP recognition and import, we have analyzed two well-studied TPs from the precursor of RuBisCO small subunit （SStp） and ferredoxin （Fdtp）. Both SStp and Fdtp contain two FGLK motifs. Analysis of large set mutations （-85） in these two motifs using in vitro, in organello, and in vivo approaches support a model in which the FGLK domains mediate interaction with TOC34 and possibly other TOC components. In vivo import analysis suggests that multiple FGLK motifs are functionally redundant. Furthermore, we discuss how FGLK motifs are required for efficient precursor protein import and how these elements may permit a convergent function of this highly variable class of targeting sequences.

关键词： chloroplast biology protein translocation Toc34 transit peptide cell biology

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Ancient DNA reveals the maternal genetic history of East Asian domestic pigs

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Journal of Genetics and genomics 2022年第6期49卷 537-546页

作者： Ming Zhang Yichen Liu Zhipeng Li Peng Lü Jacob D.Gardner Maolin Ye Jihuai Wang Miaomiao Yang Jing Shao Weilin Wang Qingyan Dai Peng Cao Ruowei Yang Feng Liu Xiaotian Feng Lizhao Zhang Enwei Li Yunzheng Shi Zehui Chen Shilun Zhu Weiwei Zhai Tao Deng Ziyuan Duan E.Andrew Bennett Songmei Hu Qiaomei Fu Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyCenter for Excellence in Life and PaleoenvironmentChinese Academy of SciencesBeijing 100044China Shanghai Qi Zhi Institute Shanghai 200232China Institute of Archaeology Chinese Academy of Social SciencesBeijing 100710China School of History and Culture Lanzhou UniversityLanzhouGansu 730000China Shaanxi Academy of Archaeology Xi’anShaanxi 710054China School of History and Culture Shanxi UniversityTaiyuanShanxi 030006China Xingtai Cultural Relics Administration XingtaiHebei 054000China Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Zoo-archaeological and genetic evidence suggest that pigs were domesticated independently in Central China and Eastern Anatolia along with the development of agricultural communities and ***,the genetic history of domestic pigs,especially in China,has not been fully *** this study,we generate 42 complete mitochondrial DNA sequences from~7500-to 2750-year-old individuals from the Yellow River *** results show that the maternal genetic continuity of East Asian domestic pigs dates back to at least the Early to Middle *** contrast,the Near Eastern ancestry in European domestic pigs saw a near-complete genomic replacement by the European wild *** majority of East Asian domestic pigs share close haplotypes,and the most recent common ancestor of most branches dates back to less than 20,000 years before present,inferred using new substitution rates of whole mitogenomes or combined protein-coding *** major population expansion events of East Asian domestic pigs coincided with changes in climate,widespread adoption of introduced crops,and the development of agrarian *** findings add to our understanding of the maternal genetic composition and help to complete the picture of domestic pig evolutionary history in East Asia.

关键词： Ancient mitogenomes Sus scrofa Pig domestication Genetic history East Asia

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Systems Pharmacological Approach to Investigate the Mechanism of Hericium erinaceus for Alzheimer’s Disease

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Digital Chinese Medicine 2019年第1期2卷 7-18页

作者： SONG Zhen-Yan CHENG Shao-Wu Institute of Nutritional Sciences Laboratory for Nutrition in Prevention and TherapyJustus-Liebig-University of GiessenBiomedical Research Center Seltersberg (BFS)Giessen 35390Germany The Key Laboratory of Hunan Province far Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases Hunan University of Chinese MedicineChangshaHunan 410208China

Objective To confirm evidence regarding the potential therapeutic effect of Hericium erinaceus(***,Hou Tou Gu,猴头菇) on Alzheimer’s disease(AD) using a system pharmacological approach in *** The active compounds of *** were screened from the TCMDatabase@Taiwan,PubMed,and *** predicted targets of *** were selected by using the Similarity Ensemble Approach Database and the DisGeNET database was used to screen the targets related to *** compound-target-AD network was *** analysis and Pathway enrichment analysis were used for bioinformatics *** A total of 21 kinds of *** active compounds were screened by network pharmacology,showing 451 predicted targets of active *** them,165 targets were associated with AD,and the compounds in *** were highly connected to AD-related signaling pathways and biological processes,such as cholinergic synaptic transmission,inflammation-related pathways and neurotrophin signaling *** Our results indicate that compounds in *** interact with multiple targets in a synergetic way and the anti-inflammatory,anti-apoptosis and synaptic transmission enhancing effects of *** might contribute to its major therapeutic effects on Alzheimer’s disease.

关键词： Systems pharmacology Hericium erinaceus(Hou Tou Gu,猴头菇) Alzheimer's disease In silico

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Gut microbiota,inflammation,and molecular signatures of host response to infection

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Journal of Genetics and genomics 2021年第9期48卷 792-802页

作者： Wanglong Gou Yuanqing Fu Liang Yue Geng-Dong Chen Xue Cai Menglei Shuai Fengzhe Xu Xiao Yi Hao Chen Yi Zhu Mian-Li Xiao Zengliang Jiang Zelei Miao Congmei Xiao Bo Shen Xiaomai Wu Haihong Zhao Wenhua Ling Jun Wang Yu-Ming Chen Tiannan Guo Ju-Sheng Zheng College of Life Sciences Zhejiang UniversityHangzhou 310058China Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province School of Life SciencesWestlake UniversityHangzhou 310024China center for Infectious Disease Research Westlake Laboratory of Life Sciences and BiomedicineHangzhou 310024China Institute of Basic Medical Sciences Westlake Institute for Advanced StudyHangzhou 310024China Key Laboratory of Structural Biology of Zhejiang Province School of Life SciencesWestlake UniversityHangzhou 310024China Guangdong Provincial Key Laboratory of Food Nutrition and HealthDepartment of EpidemiologySchool of Public HealthSun Yat-sen UniversityGuangzhou 510275China Taizhou Hospital Wenzhou Medical UniversityLinhai 325035China CAS Key Laboratory for Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

Gut microbial dysbiosis has been linked to many noncommunicable ***,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to ***,we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers,which have recently been identified as molecular signatures predicting the progression of the *** demonstrate that in our cohort of 990 healthy individuals without infection,this proteomic risk score is positively associated with proinflammatory cytokines mainly among older,but not younger,*** further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 *** metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and ***,our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy *** results may provide novel insights into the cross-talk between gut microbiota and host immune system.

关键词： Gut microbiota Proinflammatory cytokines Proteomic biomarkers COVID-19 Host infection response

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Monsoon boosted radiation of the endemic East Asian carps

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Science China(Life Sciences) 2023年第3期66卷 563-578页

作者： Chenguang Feng Kun Wang Wenjie Xu Liandong Yang Kunyuan Wanghe Ning Sun Baosheng Wu Feixiang Wu Lei Yang Qiang Qiu Xiaoni Gan Yiyu Chen Shunping He State Key Laboratory of Freshwater Ecology and Biotechnology Institute of HydrobiologyChinese Academy of SciencesWuhan 430072China School of Ecology and Environment Northwestern Polytechnical UniversityXi'an 710072China Key Laboratory of Adaptation and Evolution of Plateau Biota of Chinese Academy of Sciences Northwest Institute of Plateau BiologyChinese Academy of SciencesXining 810008China University of Chinese Academy of Sciences Beijing 100039China Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China Florida Museum of Natural History University of FloridaGainesvilleFL 32611USA National Natural Science Foundation of China Beijing 100085China center for Excellence in Animal Evolution and Genetics Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China

Major historical events often trigger the rapid flourishing of a few lineages,which in turn shape established biodiversity *** did this process occur and develop?This study provides a window into this *** endemic East Asian carps(EEAC)dominated the ichthyofauna of East Asia and exhibited a high degree of adaptation to monsoonal river-lake ecosystems.A series of evidence,including ecogeography,phylogenetics,and macroevolution,suggests that the EEAC is a lineage that arose with the East Asian monsoon and thrived intimately with subsequent monsoon *** further deduce the evolution of the EEAC and find that a range of historical events in the monsoon setting(e.g.,marine transgression and regression and glacial-interglacial cycle)have further reshaped the distribution patterns of EEAC’s *** genomics analyses reveal that introgressions during the initial period of EEAC radiation and innovations in the regulation of the brain and nervous system may have aided their adaptation to river-lake ecosystems in a monsoon setting,which boosted ***,this study strengthens knowledge of the evolutionary patterns of freshwater fishes in East Asia and provides a model case for understanding the impact of major historical events on the evolution of biota.

关键词： adaptive radiation Xenocyprididae east Asian monsoon genomes macroevolution phylogenomics

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Precision health: A nursing perspective

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International Journal of Nursing Sciences 2020年第1期7卷 5-12页

作者： Mei R.Fu Emma Kurnat-Thoma Angela Starkweather Wendy A.Henderson Ann K.Cashion Janet K.Williams Maria C.Katapodi Karin Reuter-Rice Kathleen T.Hickey Veronica Barcelona de Mendoza Kathleen Calzone Yvette P.Conley Cindy M.Anderson Debra E.Lyon Michael T.Weaver Pamela K.Shiao Rose E.Constantino Shu-Fen Wung Marilyn J.Hammer Joachim G.Voss Bernice Coleman William F.Connell School of Nursing Boston CollegeChestnut HillMAUSA National Institute of Nursing Research National Institutes of HealthBethesdaMDUSA School of Nursing and Health Studies Georgetown UniversityWashingtonDCUSA School of Nursing University of ConnecticutStorrsCTUSA School of Nursing The University of IowaIowa CityIAUSA Nursing Science University of BaselBaselSwitzerland School of Nursing Duke UniversityDurhamNCUSA School of Nursing Columbia UniversityNew YorkNYUSA School of Nursing Yale UniversityOrangeCTUSA National Cancer Institute Center for Cancer ResearchGenetic BranchBethesdaMDUSA School of Nursing University of PittsburghPittsburghPAUSA College of Nursing The Ohio State UniversityOHUSA University of Florida Gainesville FLUSA center for Biotechnology and Genomic Medicine Medical College of GeorgiaAugusta UniversityAugustaGAUSA College of Nursing The University of Arizona TucsonAZUSA Dana-Farber Cancer Institute 450 Brookline AvenueLW523BostonMAUSA Frances Payne Bolton School of Nursing Case Western Reserve UniversityClevelandOHUSA Nursing Research and Development Cedars-Sinai Medical CenterLos AngelesUSA

Precision health refers to personalized healthcare based on a person's unique genetic,genomic,or omic composition within the context of lifestyle,social,economic,cultural and environmental influences to help individuals achieve well-being and optimal *** health utilizes big data sets that combine omics(*** sequence,protein,metabolite,and microbiome information)with clinical information and health outcomes to optimize disease diagnosis,treatment and prevention specific to each *** implementation of precision health requires interprofessional collaboration,community outreach efforts,and coordination of care,a mission that nurses are well-positioned to *** the surge of interest and attention to precision health,most nurses are not well-versed in precision health or its implications for the nursing *** on a critical analysis of literature and expert opinions,this paper provides an overview of precision health and the importance of engaging the nursing profession for its *** topics reviewed in this paper include big data and omics,information science,integration of family health history in precision health,and nursing omics research in symptom *** paper concludes with recommendations for nurse leaders in research,education,clinical practice,nursing administration and policy settings for which to develop strategic plans to implement precision health.

关键词： Nurses genomics Omics Precision medicine Precision health

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