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Structure of African swine fever virus p15 reveals its dual role for membrane-association and DNA binding

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Protein & Cell 2020年第8期11卷 606-612页

作者： Dan Fu Dongming Zhao Wei Zhang Guangshun Zhang Mingyu Li Zheng Zhang Yuhui Wang Dongdong Sun Peng Jiao Cheng Chen Yu Guo zihe rao State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai UniversityTianjin 300350People's Republic of China State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150001People's Republic of China School of Life Sciences Tianjin UniversityTianjin 300071People's Republic of China

Dear Editor, African swine fever (ASF) is a highly contagious disease of domestic pigs caused by African swine fever virus (ASFV),with mortality rates approaching 90%-100%.The first ASF case was described in 1921 in *** the past decades, ASF has spread from Sub-Saharan Africa to Europe and Asia, and pose a huge threat to global food *** the first ASF case reported in August 2018, more than 10 million pigs had been culled in China at an enormous economic *** risk of ASFV mutating to infect humans is extremely ***, ASF not only threatens food security but also severely strikes the world economy in many fields, such as the global supply of the blood thinner heparin,most of which is produced from ***, ASF is a strictly monitored infectious animal disease by OIE (World Organization for Animal Health), unfortunately, there is no approved drug or vaccine against this lethal viral disease.

关键词： swine fever African

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近期国外重要的生命科学研究计划和资助情况

中国科学基金 2006年第5期20卷 272-277页

作者：饶子和中国科学院生物物理研究所

人类基因组计划的开展、实施和顺利完成,标志着生命科学开始由以自由探索为特点的“小科学”时代逐步进入了以学科交叉为特点,以国家战略需求与国际科学前沿为目标的“大科学”时代,且“大科学”与“小科学”结合、互补,同时并存。由于... 详细信息

人类基因组计划的开展、实施和顺利完成,标志着生命科学开始由以自由探索为特点的“小科学”时代逐步进入了以学科交叉为特点,以国家战略需求与国际科学前沿为目标的“大科学”时代,且“大科学”与“小科学”结合、互补,同时并存。由于“大科学”是要发挥多学科交叉、优势互补、组织团队、联合攻关去完成某一项科学计划或科学工程,因此需要得到国家、政府和相关部门的宏观调控和资金方面的支持。本文将对美国、英国和日本近期实施的一些重要的生命科学研究计划和资助情况进行调研,以了解和掌握国际生命科学的发展方向。

关键词： “大科学” 生命科学研究计划资助情况

Crystal structure of human Gadd45 reveals an active dimer

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Protein & Cell 2011年第10期2卷 814-826页

作者： Wenzheng Zhang Sheng Fu Xuefeng Liu Xuelian Zhao Wenchi Zhang Wei Peng Congying Wu Yuanyuan Li Xuemei Li Mark Bartlam Zong-Hao Zeng Qimin Zhan zihe rao National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Tianjin Key Laboratory of Protein Science College of Life SciencesNankai UniversityTianjin 300071China Laboratory of Structural Biology Tsinghua UniversityBeijing 100084China State Key Laboratory of Molecular Oncology Cancer InstituteChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

The human Gadd45 protein family plays critical roles in DNA repair,negative growth control,genomic stability,cell cycle checkpoints and *** we report the crystal structure of human Gadd45,revealing a unique dimer formed via a bundle of four parallel helices,involving the most conserved residues among the Gadd45 *** analysis of human Gadd45 identified a conserved,highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen(PCNA),p21 and cdc2,suggesting that the parallel dimer is the active form for the *** assays indicate that:(1)dimerization of Gadd45 is necessary for apoptosis as well as growth inhibition,and that cell growth inhibition is caused by both cell cycle arrest and apoptosis;(2)a conserved and highly acidic patch on the dimer surface,including the important residues Glu87 and Asp89,is a putative interface for binding proteins related to the cell cycle,DNA repair and *** results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.

关键词： crystal structure Gadd45 dimer DNA repair growth inhibition apoptosis

Preparation of the selenome-thionine derivative of tab-toxin resistance protein

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Chinese Science Bulletin 2001年第15期46卷 1304-1307页

作者： HE Hongzhen SHAO Yu CHEN Yuhang LIU Bingbing CAO Zhenbo JIANG Fan LIU Yiwei TANG Hong LIU Jinyuan ZHAO Nanming rao zihe Laboratory of Structural Biology&Protein Science Laboratory of MOE School of Life Science and EngineeringTsinghua UniversityBeijing 100084China

In order to obtain phase information for the X-ray diffraction of tabtoxin resistance protein (TTR) crystal using the MAD phasing method, a selenomethionine (Se-Met) derivative of TTR was overexpressed in E. coli strain M15, with pQE-30 plasmid, through IPTG induction in M9 medium containing Se-Met. The product was purified to an estimated homogeneity of greater than 95% according to SDS-PAGE, by a Ni-NTA metal affinity followed by a Mono Q anion exchange column chromatography. The successful substitution of Se-Met for methionine (Met) was confirmed by MALDI-TOF and ESI-Quadrupole Mass Spectrometry analysis. The derivative crystal was obtained using similar conditions as those for the native.

关键词： Se-Met TTR derivative expression purification mass spectrometry.

Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB

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Protein & Cell 2023年第6期14卷 448-458页

作者： Shan Sun Yan Gao Xiaolin Yang Xiuna Yang Tianyu Hu Jingxi Liang Zhiqi Xiong Yuting Ran Pengxuan Ren Fang Bai Luke WGuddat Haitao Yang zihe rao Bing Zhang Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Medicinal Chemical Biology Nankai UniversityTianjin 300353China Laboratory of Structural Biology Tsinghua UniversityBeijing 100084China National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China School of Chemistry and Molecular Biosciences The University of QueenslandBrisbaneQueensland 4072Australia CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100101China Shanghai Clinical Research and Trial Center Shanghai 201210China

The adenosine 5'-triphosphate(ATP)-binding cassette(ABC)transporter,IrtAB,plays a vital role in the replication and viability of Mycobacterium tuberculosis(Mtb),where its function is to import iron-loaded ***,it adopts the canonical type IV exporter ***,we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP,ADP,or ATP analogue(AMP-PNP)at resolutions ranging from 2.8 to 3.5Å.The structure of IrtAB bound ATP-Mg2+shows a“head-to-tail”dimer of nucleotide-binding domains(NBDs),a closed amphipathic cavity within the transmembrane domains(TMDs),and a metal ion liganded to three histidine residues of IrtA in the ***-electron microscopy(Cryo-EM)structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with ***,the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport *** study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.

关键词： ABC exporter-like importer iron-loaded siderophore IrtAB Mycobacterium tuberculosis ABC transporter

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加紧实施“战略性基础研究计划”

科技导报 2022年第6期40卷 1-2页

作者：饶子和清华大学北京100084

基础研究是科技创新的源泉。党的十八大以来,习近平总书记多次强调基础研究的重要意义,提出“基础研究是整个科学体系的源头,是所有技术问题的总机关”的重要论断,为发展基础研究指明了方向。特别是《中共中央关于制定国民经济和社会发... 详细信息

基础研究是科技创新的源泉。党的十八大以来,习近平总书记多次强调基础研究的重要意义,提出“基础研究是整个科学体系的源头,是所有技术问题的总机关”的重要论断,为发展基础研究指明了方向。特别是《中共中央关于制定国民经济和社会发展第十四个五年规划和二〇三五年远景目标的建议》,把“坚持创新”放在“十四五”工作的首位,是“五年规划建议”历史上第一次以专章部署“创新”。

关键词：远景目标五年规划党的十八大以来坚持创新战略性基础研究习近平总书记

Crystal structure of the African swine fever virus structural protein p35 reveals its role for core shell assembly

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Protein & Cell 2020年第8期11卷 600-605页

作者： Guobang Li Dan Fu Guangshun Zhang Dongming Zhao Mingyu Li Xue Geng Dongdong Sun Yuhui Wang Cheng Chen Peng Jiao Lin Cao Yu Guo zihe rao State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai UniversityTianjin 300350China State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150001China School of Life Sciences Tianjin UniversityTianjin 300071China

Dear Editor,The African swine fever(ASF)is a highly contagious hemorrhagic and lethal disease in domestic *** ASF outbreaks of in many Asia countries,including China,Vietnam,Mongolia,and South Korea,have posed a huge threat to the pig *** the attempt to stop ASF from spreading further in China's Mainland,more than 10 million pigs have been culled since August *** causative agent for ASF is a DNA virus,African swine fever virus(ASFV).Although this deadly disease has been reported in Kenya nearly one hundred years ago,there has been no vaccine for protection from ASFV infection or effective treatments to cure ASF until now.

关键词： swine fever African

Discovery of the first macrolide antibiotic binding protein in Mycobacterium tuberculosis： a new antibiotic resistance drug target

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Protein & Cell 2018年第11期9卷 971-975页

作者： Qingqing Zhang Huijuan Liu Xiang Liu Dunquan Jiang Bingjie Zhang Hongliang Tian Cheng Yang Luke W. Guddat Haitao Yang Kaixia Mi zihe rao College of Life Sciences Nankai University Tianjin 300071 China College of Pharmacy Nankai University Tianjin 300071 China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing100101 China School of Life Sciences Tianjin University Tianjin 300072 China School of Chemistry and Molecular Biosciences The University ofQueensland Brisbane QLD 4072 Australia Laboratory of Structural Biology School of Medicine TsinghuaUniversity Beijing 100084 China Tianjin International Joint Academy of Biotechnology & Medicine Tianjin 300457 China

Dear Editor The prevalence of multidrug-resistant Mycobacterium tuberculosis （M. tuberculosis） is an increasing problem worldwide （Zumla et al., 2013; Dong et al., 2015）. According to a 2014 World Health Organization （WHO） report, 480,000 individuals world-wide .developed multidrug-resistant tuber- culosis （MDR-TB） and more than 100 countries have cases of extensively drug-resistant tuberculosis （XDR-TB）. Com- pared with drug-susceptible TB, MDR-TB and XDR-TB require prolonged therapeutic treatment with a combination of a number of second-line drugs （Chen et al., 2013）. For patients where TB remains persistent despite prolonged therapy with second-line TB drugs, the add-on agents including bedaquiline and delamanid are recommended for salvage therapy （GUnther, 2014; WHO, 2014; Shim and Jo, 2013）.

关键词： MOLECULAR-MECHANISMS ABC

Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization

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Protein & Cell 2016年第7期7卷 516-526页

作者： Jiao Wang Zhizhi Wang Tingting Yu Huan Yang David M. Virshup Geert J. P. L. Kops Sang Hyun Lee Weihong Zhou Xin Li Wenqing Xu zihe rao College of Life Sciences Nankai University Tianjin 30071 China Department of Biological Structure University of Washington Seattle WA 98195 USA Program in Cancer and Stem Cell Biology Duke-NUS Graduate Medical School 8 College Road Singapore 169857 Singapore Department of Pediatrics Duke University Medical Center Durham NC 27710 USA Molecular Cancer Research and Cancer-Genomics Centre and Department of Medical Oncology UMC Utrecht Universiteitsweg 100 3584 CG Utrecht The Netherlands National Laboratory of Macromolecutes Institute of Biophysics Chinese Academy of Sciences Beijing 100010 China

Protein phosphatase 2A （PP2A） accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a cat- alytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kine- tochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interac- tion plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attach- ment. Here we present the crystal structure of a PP2A B56-BubRI complex, which demonstrates that a con- served BubRl LxxlxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxlxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.

关键词： PP2A BubR1 kinetochore cellulartargeting substrate recruitment