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| 1 | 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 |
| 2 | Synthesis of nearly spherical AlN particles by an in-situ nitriding combustion route显示文摘Spherical AlN powders with micrometer size have attracted great attention owing to their good fluidity and dispersity. However, the industrial preparation methods usually require high temperature and long soaking time, which lead to the high cost and limit the wide application of the products. Herein, nearly spherical AlN particles with the average size of 2.5 μm were successfully synthesized via an in-situ combustion synthesis method. The effect of N_(2) pressure, NH_(4)Cl content, and Al particle size on the combustion reaction procedure, phase composition, and microstructure of the products was systematically investigated. The results showed that the decreased N_(2) pressure, increased NH_(4)Cl content, and Al particle size led to the decreasing of combustion temperature and speed, which further affected the morphology of the products. As a result, low N_(2) pressure(0.2 MPa), a small amount of NH4Cl(0.5 wt%), and fine Al particles(~2.5 μm) contributed to a moderate combustion temperature and facilitated the formation of nearly spherical AlN particles. In addition, based on the gas-releasing assisted quenching experiments and thermo-kinetic analysis, a two-step growth mechanism for the nearly spherical AlN particles was rationally proposed. The present method shows the advantages of low cost and high efficiency for preparing nearly spherical AlN particles, which can be used as raw materials for electronic substrates and fillers for packaging materials. | Zhilei Wei Kang Li Bangzhi Ge Chaowei Guo Hongyan Xia Yajie Guo Zhongqi Shi | 2021 | Journal of Advanced Ceramics2021，10，2： | 2 |
| 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 | 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 |
| 5 | 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 |
| 6 | Effi cient long-distance NMR-PRE and EPR-DEER restraints for two-domain protein structure determination显示文摘Dear Editor,The functional diversity of proteins is related to the cooperation of multiple domains.Independent globular domains are typically joined by a fl exible length of polypeptide chain,which makes the structural analysis of multi-domain proteins diffi cult.Here,we describe the combined use of solution NMR(nuclear magnetic resonance)and EPR(elec-tron paramagnetic resonance)for the structural analysis of a protein with two separate domains.The structure of each domain was determined independently using conventional NMR restraints,and the relative orientation of the two separate domains was confi ned using long-distance restraints obtained by NMR-PRE(paramagnetic relaxation enhancement)and EPR-DEER(double electron-electron resonance,also called PELDOR:pulsed electron double reso-nance. | Kaiqi Wu Chaowei Shi Juan Li Haipeng Wang Pan Shi Liu Chen Fangming Wu Ying Xiong Changlin Tian | 2013 | Protein & Cell2013，4，12： | 0 |
| 7 | Allosteric conformational changes of G proteins upon its interaction with membrane and GPCR显示文摘Current resolved structures of GPCRs and G protein complexes provided important insights into G protein activation. However, the binding or dissociation of GPCRs with G protein is instantaneous and highly dynamic in the intracellular environment. The conformational dynamic of G protein still needs to be addressed. In this study, we applied ^(19)F solution NMR spectroscopy to monitor the conformational changes of G protein upon interact with detergent mimicking membrane and receptor. Our results show that there are two states equilibria in the G_(α)in apo states. The interaction of G_(α)with detergents will accelerate this conformational transformation and induce a state that tends to bind to GPCRs. Finally, the G_(α)proteins presented a fully activation state when they coupled to GPCRs. | Longmei Li Jin Zhang Wenjing Sun Weimin Gong Changlin Tian Pan Shi Chaowei Shi | 2022 | Chinese Chemical Letters2022，33，2： | 0 |
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