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| 1 | Coagulation factors VII, IX and X are effective antibacterial proteins against drug-resistant Gram-negative bacteria显示文摘Infections caused by drug-resistant“superbugs”pose an urgent public health threat due to the lack of effective drugs;however, certain mammalian proteins with intrinsic antibacterial activity might be underappreciated. Here, we reveal an antibacterial property against Gram-negative bacteria for factors VII, IX and X, three proteins with well-established roles in initiation of the coagulation cascade. These factors exert antibacterial function via their light chains (LCs). Unlike many antibacterial agents that target cell metabolism or the cytoplasmic membrane, the LCs act by hydrolyzing the major components of bacterial outer membrane, lipopolysaccharides, which are crucial for the survival of Gram-negative bacteria. The LC of factor VII exhibits in vitro efficacy towards all Gram-negative bacteria tested, including extensively drug-resistant (XDR) pathogens, at nanomolar concentrations. It is also highly effective in combating XDR Pseudomonas aeruginosa and Acinetobacter baumannii infections in vivo. Through decoding a unique mechanism whereby factors VII, IX and X behave as antimicrobial proteins, this study advances our understanding of the coagulation system in host defense, and suggests that these factors may participate in the pathogenesis of coagulation disorder-related diseases such as sepsis via their dual functions in blood coagulation and resistance to infection. Furthermore, this study may offer new strategies for combating Gram-negative “superbugs”. | Jinwu Chen Xiaojie Li Ling Li Ting Zhang Qing Zhang Fangming Wu Diyue Wang Hongze Hu Changlin Tian Dongsheng Liao Liang Zhao Danxia Song Yongyun Zhao Chuanfang Wu Xu Song | 2019 | Cell Research2019，29，9： | 6 |
| 2 | Structural mechanism of cooperative activation of the human calcium-sensing receptor by Ca^(2+) ions and L-tryptophan显示文摘The human calcium-sensing receptor(CaSR)is a class C G protein-coupled receptor(GPCR)responsible for maintaining Ca^(2+)homeostasis in the blood.The general consensus is that extracellular Ca^(2+)is the principal agonist of CaSR.Aliphatic and aromatic L-amino acids,such as L-Phe and L-Trp,increase the sensitivity of CaSR towards Ca^(2+)and are considered allosteric activators.Crystal structures of the extracellular domain(ECD)of CaSR dimer have demonstrated Ca^(2+)and L-Trp binding sites and conformational changes of the ECD upon Ca^(2+)/L-Trp binding.However,it remains to be understood at the structural level how Ca^(2+)/L-Trp binding to the ECD leads to conformational changes in transmembrane domains(TMDs)and consequent CaSR activation.Here,we determined the structures of full-length human CaSR in the inactive state,Ca^(2+)-or L-Trp-bound states,and Ca^(2+)/L-Trp-bound active state using single-particle cryo-electron microscopy.Structural studies demonstrate that L-Trp binding induces the closure of the Venus flytrap(VFT)domain of CaSR,bringing the receptor into an intermediate active state.Ca^(2+)binding relays the conformational changes from the VFT domains to the TMDs,consequently inducing close contact between the two TMDs of dimeric CaSR,activating the receptor.Importantly,our structural and functional studies reveal that Ca^(2+)ions and L-Trp activate CaSR cooperatively.Amino acids are not able to activate CaSR alone,but can promote the receptor activation in the presence of Ca^(2+).Our data provide complementary insights into the activation of class C GPCRs and may aid in the development of novel drugs targeting CaSR. | Shenglong Ling Pan Shi Sanling Liu Xianyu Meng Yingxin Zhou Wenjing Sun Shenghai Chang Xing Zhang Longhua Zhang Chaowei Shi Demeng Sun Lei Liu Changlin Tian | 2021 | Cell Research2021，31，4： | 3 |
| 3 | Cryo-EM structure of the hyperpolarization-activated inwardly rectifying potassium channel KAT1 from Arabidopsis显示文摘Dear Editor,Plants utilize K^+ions to maintain hydrostatic pressure,drive irreversible cell expansion for growth,and facilitate reversible changes in guard cell volume that cause stomatal opening or closing.KAT1 is a voltage-dependent potassium channel from Arabidopsis thaliana that is mainly expressed in guard cells.KAT1 allows the influx of K+,leading to the swelling and opening of the stoma,and therefore plays a key role in regulating the aperture of stomatal pores on the surface of plant leaves. | Siyu Li Fan Yang Demeng Sun Yong Zhang Mengge Zhang Sanling Liu Peng Zhou Chaowei Shi Longhua Zhang Changlin Tian | 2020 | Cell Research2020，30，11： | 2 |
| 4 | Chemical synthesis of Ub-AMC via ligation of peptide hydrazides显示文摘The C-terminal conjugate of ubiquitin with 7-amino-4-methylcoumarin (Ub-AMC) is an important probe for fluorescencebased analysis of deubiquitinating enzyme (DUB) activity. It is important to develop more efficient methods for the preparation of Ub-AMC because the currently available technology is still expensive for scaled-up production. In the present work we report an efficient strategy for total chemical synthesis of Ub-AMC through ligation of peptide hydrazides. Three peptide segments are assembled via N-to-C sequential ligation and the resulting product is converted to Ub-AMC via TCEP-mediated desulfurization. The synthetic Ub-AMC is shown to have expected biological functions | LIANG Jun FANG GeMin HUANG XiuLiang MEI ZiQing LI Juan TIAN ChangLin LIU Lei | 2013 | Science China Chemistry2013，56，9： | 2 |
| 5 | Protein-protein interaction analysis in crude bacterial lysates using combinational method of ^19F site-specific incorporation and ^19F NMR显示文摘 | Dong Li Yanan Zhang Yao He Chengwei Zhang Jiefei Wang Ying Xiong Longhua Zhang Yangzhong Liu Pan Shi Changlin Tian | 2017 | Protein & Cell2017，8，2： | 2 |
| 6 | MODE SPACE SMOOTHING ALGORITHM TO ESTIMATE DOA OF COHERENT SIGNALS IMPINGING ON UNIFORM CIRCULAR ARRAY显示文摘A novel method to estimate DOA of coherent signals impinging on a uniform circular array( UCA) is presented in this paper. A virtual uniform linear array (VULA) is first derived by using spatial DFT technique, transforming the UCA from element space to phase mode space to obtain the properties of ordinary ULA, and then the well known spatial smoothing technique is applied to the VULA so that the lost rank of covariance matrix due to signal coherence can be retrieved. This method makes it feasible to use the simple MUSIC algorithm to estimate DOA of coherent signals impinging on a UCA without heavy computation burden. Simulation results strongly verify the effectiveness of the algorithm. | Ma Changlin Peng Yingning Tian Lisheng Liu Jianhua(Department of Electronic Engineering, Tsinghua University, Beijing 100084) | 1998 | Journal of Electronics(China)1998，15，4： | 1 |
| 7 | Total synthesis of snake toxin α-bungarotoxin and its analogues by hydrazide-based native chemical ligation显示文摘Nicotinic acetylcholine receptors(nAChRs) play important roles in intercellular communications of nerve cells. α-Bungarotoxins(αBtx) is a moderator for the nAChRs. Chemical synthesis provides a promising way to access aBtx and their analogues. Here, we reported a new method for a-bungarotoxin by combining Fmoc-SPPS and peptide hydrazide based ligation strategy. The two-segment ligation method may enable efficient synthesis of aBtx analogues. These synthetic toxin peptides are useful tools for development of imaging or therapeutic reagents. | Xiao-Qi Guo Jun Liang Ying Li Yong Zhang Dongliang Huang Changlin Tian | 2018 | Chinese Chemical Letters2018，29，7： | 1 |
| 8 | Biochemical properties of K_(11,48)-branched ubiquitin chains显示文摘As one of the most widely existing post-translational modification models, ubiquitination regulates diverse cellular activities. In eukaryotes, K_(11,48)-branched ubiquitin chains play key roles in cell cycle and protein quality control. However, the structural and biochemical properties of K_(11,48)-branched ubiquitin chains have not been well examined. Here we employed the synthetic linkage-and length-defined K_(11,48)-branched ubiquitin chains to examine their binding and hydrolysis properties in vitro. Quantitatively affinity determination of ubiquitin chains to the proteasome ubiquitin receptor S5 a indicated that the S5 a exhibited preference binding to K_(11,48)-branched chains over K_(11)-linked chains, but not K_(48)-conjugated chains. In addition, deubiquitination experiments were carried out and the results showed that K_(11,48)-branched chains were preferably hydrolyzed by proteasome-associated deubiquitinase Rpnll than homotypic K_(11) or K_(48)-linked chains. | Lu-Jun Liang Yanyan Si Shan Tang Dongliang Huang Zhipeng A.Wang Changlin Tian Ji-Shen Zheng | 2018 | Chinese Chemical Letters2018，29，7： | 1 |
| 9 | Accumulation of tissue advanced glycation end products correlated with glucose exposure dose and associated with cardiovascular morbidity in patients on peritoneal dialysis显示文摘 | Jianping Jiang Pingyan Chen Jianghua Chen Xueqing Yu Di Xie Changlin Mei Fei Xiong Wei Shi Wei Zhou Xusheng Liu Shiren Sun Ping Zhang Xiao Yang Yixiang Zhang Yanmin Zhang Xinling Liang Zhimin Zhang Qizhan Lin Yan Yu Toshio Miyata Jianwei Tian Min Liang We | 2012 | Atherosclerosis2012，，1： | 1 |
| 10 | Chemical protein synthesis-assisted high-throughput screening strategies for D-peptides in drug discovery显示文摘D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and specificity.Recently,D-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years.One D-peptide etelcalcetide has even entered the market that targets the calcium(Ca2+)-sensing receptor(CaSR) to fight secondary hyperparathyroidism.Effective discovery and optimization of D-peptide ligands that can bind to various disease-related targets with high specificity and potency is of great importance for the development of D-peptide drugs.This review surveys the recent method development in this area especially the chemical protein synthesis-assisted high-throughput screening strategies for D-peptide ligands and their application in drug discovery. | Ying Li Xiuxiu Cao Changlin Tian Ji-Shen Zheng | 2020 | Chinese Chemical Letters2020，31，9： | 1 |
| 11 | Chemically synthesized histone H2A Lys13 di-ubiquitination promotes binding of 53BP1 to nucleosomes显示文摘 | Jia-Bin Li Yun-Kun Qi Qiao-Qiao He Hua-Song Ai San-ling Liu Jia-Xing Wang Ji-Shen Zheng Lei Liu Changlin Tian | 2018 | Cell Research2018，28，2： | 1 |
| 12 | Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response显示文摘FANCM/FAAP24 heterodimer 在保护房间免受象 interstrand 交叉连接那样的复杂 DNA 损害的伤害有不同功能。这些功能依靠 FANCM/FAAP24 的生物化学的活动认出并且绑在损坏 DNA 或阻止的复制叉。然而,这建筑群的 DNA 有约束力的活动清楚地没被定义。我们调查了 FAAP24 怎么由获得人的 FAAP24 的 N 终端和 C 终端解决方案结构贡献 FANCM/FAAP24 建筑群的交往 DNA 函数。FAAP24 结构当模特儿显示 FAAP24 可以向搁浅单人赛的 DNA (ssDNA ) 拥有一种高亲密关系。在 vitro 并且在 vivo 各种各样的 FAAP24 变化测试验证了从结构的分析导出的这预言。我们发现 DNA 有约束力并且尽管两个要求 C 终端(HhH )2 领域, FAAP24 的交往 FANCM 功能能被 segregation-of-function 变化区分。这些结果证明在 DNA 的 FAAP24 的双角色对 crosslinking 损害损坏反应,通过经由它的 ssDNA 有约束力的活动的 FANCM/FAAP24 heterodimer 和其它的形成的在优化检查点激活要求了。 | Yucai Wang Xiao Han Fangming Wu Justin W Leung Megan G Lowery Huong Do Junjie Chen Chaowei Shi Changlin Tian Lei Li Weimin Gong | 2013 | Cell Research2013，23，10： | 1 |
| 13 | Nano-size uni-lamellar lipodisq improved in situ auto-phosphorylation analysis of E. coli tyrosine kinase using 19F nuclear magnetic resonance显示文摘亲爱的编辑, | Dong Li(1) Juan Li(1) Yonglong Zhuang(3) Longhua Zhang(1) Ying Xiong(1) Pan Shi (2) Changlin Tian (1)(2) | 2015 | Protein & Cell2015，6，3： | 1 |
| 14 | In cell measurement of fluorescence lifetime imaging microscopy revealed C-terminal conformation changes of Ferroportin upon addition of Mn^2+显示文摘Fluorescence microscopy, as a sensitive method to detect microenvironment of molecules, is widely used in protein conformation and dynamic studies in live cells. Fluorescence lifetime imaging microscopy(FLIM), which is independent of fluorophore concentrations, scattering and bleaching, is a suitable tool to analyze membrane proteins in a single cell. Ferroportin(FPN), a multi-ion exporter in vertebrates, was modulated by metal ions with unknown mechanism. Herein, we fused green fluorescence protein on Cterminal of FPN(FPN-eGFP) and applied fluorescence lifetime to monitor conformation changes of FPN in a live cell. The fluorescence lifetime distribution showed a shift to shorter lifetime upon Mn^(2+) treatment,suggesting a preference conformation of FPN in Mn^(2+) exposure. It is also observed that the lifetime(rather than intensity) measurement was not strongly influenced by laser power. The observed fluorescence lifetime changes of FPN-eGFP upon Mn^(2+) treatments indicated that extracellular metal ions can modulate FPN through conformation exchanges between several different states. | Mengge Zhang Ming Wen Ying Xiong Longhua Zhang Changlin Tian | 2018 | Chinese Chemical Letters2018，29，10： | 1 |
| 15 | Conformational change of E.coli sulfurtransferase YgaP upon SCN- in intact native membrane revealed by fluorescence lifetime and anisotropy显示文摘Fluorescence lifetime and anisotropy has become a prevalent tool to detect the structure change and motility property of proteins. YgaP is the only membrane-integrated rhodanese in E. coli. The sulfur transfer process has been characterized by various studies. However, the mechanism of the outward transportation of SCN^- remains unclear. In this work, we examined the fluorescence lifetime and anisotropy of site-specific incorporated unnatural amino acid 7-HC to study the conformational change of YgaP upon SCN^- binding. We also compared the fluorescence changes between detergent-wrapped environment in DPC and intact native membrane environment in SMA. Our results suggested the presence of at least two different conformations in YgaP protein. Both the residues in the middle of TMH2 and the residues near extracellular side play important roles in the binding and/or output of SCN^-. SMA is a good material to reflect the in situ conformation changes of protein than micelles. | Simeng Wang Yanan Zhang Longhua Zhang Min Zhang Changlin Tian | 2018 | Chinese Chemical Letters2018，29，10： | 1 |
| 16 | Structural insights into thyrotropin-releasing hormone receptor activation by an endogenous peptide agonist or its orally administered analogue显示文摘Dear Editor,Thyrotopin-releasing hormone(TRH)is a tripeptide(u pyroglu-tamyl-histidinyl-prolinamide)that is widely distributed in the brain and spinal cord,playing dual roles as both an endocrine hormone and a neuropeptide.TRH plays a central role in the hypothalamic-pituitary-thyroid(HPT)axis1-3 TRH is mainly synthesized in the hypothalamus and stimulates the release of thyroid-stimulating hormone(TSH,also known as thyrotropin)and prolactin from the anterior lobe of the hypophysis. | Fan Yang Huanhuan Zhang Xianyu Meng Yingge Li Yingxin Zhou Shenglong Ling Demeng Sun Pei Lv Lei Liu Pan Shi Changlin Tian | 2022 | Cell Research2022，32，9： | 0 |
| 17 | Structural insights into asymmetric activation of the calcium-sensing receptor–G_(q) complex显示文摘Dear Editor,The human calcium-sensing receptor(CaSR)is a class C G protein-coupled receptor(GPCR)responsible for maintaining Ca^(2+)homeostasis in blood.^(1,2) In normal physiological processes,in response to extracellular stimuli,CaSR can activate multiple intracellular signaling pathways involving G_(q),G_(i) or G_(12/13).^(1) Dysfunctions of CaSR can lead to hypercalcaemic and hypocalcaemic disorders.^(3,4) Positive allosteric modulators(PAMs)serving as calcimimetics,namely,cinacalcet,evocalcet and etelcalcetide,were developed as drugs to treat hyperparathyroidism in patients with chronic kidney disease. | Shenglong Ling Xianyu Meng Yuan Zhang Zhemin Xia Yingxin Zhou Fan Yang Pan Shi Chaowei Shi Changlin Tian | 2024 | Cell Research2024，34，2： | 0 |
| 18 | Different conformational responses of theβ_(2)-adrenergic receptor-Gs complex upon binding of the partial agonist salbutamol or the full agonist isoprenaline显示文摘G protein-coupled receptors(GPCRs)are responsible for most cytoplasmic signaling in response to extracellular ligands with different efficacy profiles.Various spectroscopic techniques have identified that agonists exhibiting varying efficacies can selectively stabilize a specific conformation of the receptor.However,the structural basis for activation of the GPCR-G protein complex by ligands with different efficacies is incompletely understood.To better understand the structural basis underlying the mechanisms by which ligands with varying efficacies differentially regulate the conformations of receptors and G proteins,we determined the structures ofβ_(2)AR-Gαsβγbound with partial agonist salbutamol or bound with full agonist isoprenaline using single-particle cryo-electron microscopy at resolutions of 3.26?A and3.80?A,respectively.Structural comparisons between theβ_(2)AR-Gs-salbutamol andβ_(2)AR-Gs-isoprenaline complexes demonstrated that the decreased binding affinity and efficacy of salbutamol compared with those of isoprenaline might be attributed to weakened hydrogen bonding interactions,attenuated hydrophobic interactions in the orthosteric binding pocket and different conformational changes in the rotamer toggle switch in TM6.Moreover,the observed stronger interactions between the intracellular loop 2 or 3(ICL2 or ICL3)ofβ_(2)AR and Gαswith binding of salbutamol versus isoprenaline might decrease phosphorylation in the salbutamol-activatedβ_(2)AR-Gs complex.From the observed structural differences between these complexes ofβ_(2)AR,a mechanism ofβ_(2)AR activation by partial and full agonists is proposed to provide structural insights intoβ_(2)AR desensitization. | Fan Yang Shenglong Ling Yingxin Zhou Yanan Zhang Pei Lv Sanling Liu Wei Fang Wenjing Sun Liaoyuan A.Hu Longhua Zhang Pan Shi Changlin Tian | 2021 | National Science Review2021，8，9： | 0 |
| 19 | Fluorescence lifetime based distance measurement illustrates conformation changes of PYL10-CL2 upon ABA binding in solution state显示文摘Forster resonance energy transfer(FRET)is a widely used distance measurement method to illustrate protein conformational dynamics.The FRET method relies on the distance between donor and acceptor,as well as the labelling efficiency,the size and the properties of the fluorophores.Here,we labelled a pair of small fluorophores and calculated the energy transferred efficiency through fluorescence lifetime analysis,which can provide more reliable distance measurement than intensity attenuation.The donor fluorophore,7-hydroxycoumarin-4-yl-ethylglycine(HC),was genetically incorporated into specific sites of PYL10,obtaining complete labelling efficiency.The acceptor fluorophore,Alexa488,was labelled through the disulfide bond,whose labelling efficiency was estimated through both absorption peaks and lifetime populations.Fluorescence lifetime and anisotropy analysis showed ABA-induced local conformation changes and dynamics of several HC incorporation sites of PYL10.The lifetime-based FRET distance measurement illustrated the conformation changes of PYL10 with or without ABA application,which is consistent with the previously reported crystal structures. | Peng Zhou Pei Lv Lu Yu Sanling Liu Longhua Zhang Changlin Tian | 2019 | Chinese Chemical Letters2019，30，5： | 0 |
| 20 | NiH-Catalyzed Reductive Hydrocarbonation of Enol Esters and Ethers显示文摘Chiral dialkyl carbinols and their derivatives are significant synthetic building blocks in organic chemistry and related fields.The development of convenient and efficient methods to access these compounds has long been an important endeavor.Herein,we report a NiH-catalyzed reductive hydroalkylation and hydroarylation of enol esters and ethers.α-Oxoalkyl organonickel species were generated in situ in a catalytic mode and then participated in cross-coupling with alkyl or aryl halides.This approach enabled C(sp^(3))–C(sp^(3))and C(sp^(3))–C(sp^(2))bond formation under mild reductive conditions with simple operations,thereby boosting a broad substrate scope and good functional compatibility.Esters of enantioenriched dialkyl carbinols were accessed in a catalytic asymmetric version.Mechanistic studies demonstrated that this reaction proceeded through a syn-addition of Ni–H intermediate to an enol ester with high regio-and enantioselectivity. | Xiao-Xu Wang Lu Yu Xi Lu Zhi-Lin Zhang De-Guang Liu Changlin Tian Yao Fu | 2022 | CCS Chemistry2022，4，2： | 0 |
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