|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 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 | 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 |
| 3 | 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 |
| 4 | Parthenolide reveals an allosteric mode to inhibit the delSGylation activity of SARS-CoV-2 papain-like protease显示文摘The coronavirus papain-like protease(PLpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is responsible for viral polypeptide cleavage and the deISGylation of interferon-stimulated gene 15(ISG15),which enable it to participate in virus replication and host innate immune pathways.Therefore,PLpro is considered an attractive antiviral drug target.Here,we show that parthenolide,a germacrane sesquiterpene lactone,has SARS-CoV-2 PLpro inhibitory activity.Parthenolide covalently binds to Cys-191 or Cys-194 of the PLpro protein,but not the Cys-111 at the PLpro catalytic site.Mutation of Cys-191 or Cys-194 reduces the activity of PLpro.Molecular docking studies show that parthenolide may also form hydrogen bonds with Lys-192,Thr-193,and Gln-231.Furthermore,parthenolide inhibits the deISGylation but not the deubiquitinating activity of PLpro in vitro.These results reveal that parthenolide inhibits PLpro activity by allosteric regulation. | Zhihui Zou Huizhuang Shan Demeng Sun Li Xia Yulong Shi Jiahui Wan Aiwu Zhou Yunzhao Wu Hanzhang Xu Hu Lei Zhijian Xu Yingli Wu | 2022 | Acta Biochimica et Biophysica Sinica2022，54，8： | 0 |
| 5 | The putative propeptide of MycP1 in mycobacterial type VII secretion system does not inhibit protease activity but improves protein stability显示文摘Mycosin-1 protease(MycP1)is a serine protease anchored to the inner membrane of Mycobacterium tuberculosis,and is essential in virulence factor secretion through the ESX-1 type VII secretion system(T7SS).Bacterial physiology studies demonstrated that MycP1 plays a dual role in the regulation of ESX-1 secretion and virulence,primarily through cleavage of its secretion substrate EspB.MycP1 contains a putative N-terminal inhibitory propeptide and a catalytic triad of Asp-His-Ser,classic hallmarks of a sub-tilase family serine protease.The MycP1 propeptide was previously reported to be initially inactive and activated after prolonged incubation.In this study,we have deter-mined crystal structures of MycP1 with(MycP124-422)and without(MycP1^(63-422))the propeptide,and conducted EspB cleavage assays using the two proteins.Very high struc-tural similarity was observed in the two crystal structures.Interestingly,protease assays demonstrated positive EspB cleavage for both proteins,indicating that the putative propeptide does not inhibit protease activity.Molecu-lar dynamic simulations showed higher rigidity in regions guarding the entrance to the catalytic site in MycP124-422 than in MycP1^(63-422),suggesting that the putative propeptide might contribute to the conformational stability of the active site cleft and surrounding regions. | Demeng Sun Qing Liu Yao He Chengliang Wang Fangming Wu Changlin Tian Jianye Zang | 2013 | Protein & Cell2013，4，12： | 0 |
| 6 | Mutation of the critical pH-gating residues histidine 231 to glutamate increase open probability of outer membrane protein G in planar lipid bilayer显示文摘Dear Editor,Outer-membrane protein G(OmpG)is a nonspecificβ-barrel porin in the outer membrane of Escherichia coli(E.coli),allowing the passage of ions and molecules up to 900 Da(Fajardo et al.,1998).It comprises of 280 amino acids that form 14-strandedβ-sheets with seven long loops(L1-L7)on the extra-cellular side and six short turns on the periplasmic side(Subbarao and van den Berg,2006;Yildiz et al.,2006;Liang and Tamm,2007).Despite that the OmpG gene exists in the genome of several E.coli strains(Nikaido,1999),expres-sion of OmpG was only observed in E.coli mutants lacking OmpF and LamB(Fajardo et al.,1998)to enable the diffu-sion of maltodextrins across the bacte-rial outer membrane.Very interestingly,unlike usual trimeric channel-forming porins,OmpG exhibits fascinating characteristics of a functional monomer in physiological and structural studies(Conlan and Bayley,2003;Mari et al.,2010). | Mu Yu Peibei Sun Yao He Liang Xiao Demeng Sun Longhua Zhang Changlin Tian | 2013 | Protein & Cell2013，4，11： | 0 |
| 7 | Chemical Synthesis of Structurally Defined Phosphorylated Ubiquitins Suggests Impaired Parkin Activation by Phosphorylated Ubiquitins with a Non-Phosphorylated Distal Unit显示文摘Mutations in genes encoding PINK1(PTEN-induced kinase 1)and Parkin(E3 ubiquitin ligase)are identified in familial Parkinson’s disease.However,it remains unclear whether the phosphorylated Ub chains activate wild-type Parkin(w-Parkin)or phosphorylated Parkin(p-Parkin),with the consequent expulsion of the damaged mitochondria. | Man Pan Qingyun Zheng Shuai Gao Qian Qu Yuanyuan Yu Ming Wu Huan Lan Yulei Li Sanling Liu Jiabin Li Demeng Sun Lining Lu Tian Wang Wenhao Zhang Jiawei Wang Yiming Li Hong-Gang Hu Changlin Tian Lei Liu | 2019 | CCS Chemistry2019，1，5： | 0 |
| 8 | Structural basis of humanα7 nicotinic acetylcholine receptor activation显示文摘Dear Editor,Nicotinic acetylcholine receptors(nAChRs)are a class of pentameric ligand-gated ion channels(pLGICs)widely expressed in nervous system.nAChRs function as neurotransmitter receptors that respond to endogenous acetylcholine and choline,modulating neuronal excitability and synaptic communication.The homomericα7 nAChR is among the most abundant subtypes of nAChR in the brain.Dysfunction ofα7 is found to be associated with several neuropsychiatric and neurologic disorders,including schizophrenia and Alzheimer’s disease.1,2 Stimulation ofα7 has been reported to improve attention,cognitive performance,and neuronal resistance to injury.Therefore,agonists and positive allosteric modulators(PAMs)ofα7 have become hot candidates in the drug development for the treatment ofα7-related diseases.3,4 EVP-6124(abbreviated as EVP)is a high-affinityα7-selective agonist.5 PNU-120596(abbreviated as PNU)is the first reportedα7-selective PAM that could increase the peak current of the receptor evoked by agonists and delay channel desensitization.6 Both EVP and PNU are in clinical trials for the treatment of Alzheimer’s disease,schizophrenia,and cognitive impairment.Despite the significance ofα7 in physiology and pharmacology,the mechanisms underlying the activation ofα7 upon agonist and/or PAM binding remain elusive.Little is known about the structural basis of the higher selectivity of EVP and PNU forα7,which would be highly valuable for rational drug development targeting the receptor.Herein,we report the structures of full-length humanα7 in apo,EVP-bound and EVP/PNU-bound states at 3.18,2.85 and 3.02Å,respectively(Fig.1a–c;Supplementary information,Figs.S1–S4 and Table S1). | Yue Zhao Sanling Liu Yingxin Zhou Mengge Zhang Haopeng Chen HEric Xu Demeng Sun Lei Liu Changlin Tian | 2021 | Cell Research2021，31，6： | 0 |
| 9 | Scalable synthesis of lipid nanoparticles for nucleic acid drug delivery using an isometric channel-size enlarging strategy显示文摘Lipid nanoparticles(LNPs)have emerged as highly effective delivery systems for nucleic acid-based therapeutics.However,the broad clinical translation of LNP-based drugs is hampered by the lack of robust and scalable synthesis techniques that can consistently produce formulations from early development to clinical application.In this work,we proposed a method to achieve scalable synthesis of LNPs by scaling inertial microfluidic mixers isometrically in three dimensions.Moreover,a theoretical predictive method,which controls the mixing time to be equal across different chips,is developed to ensure consistent particle size and size distribution of the synthesized LNPs.LNPs loaded with small interfering RNA(siRNA)were synthesized at different flow rates,exhibiting consistent physical properties,including particle size,size distribution and encapsulation efficiency.This work provides a practical approach for scalable synthesis of LNPs consistently,offering the potential to accelerate the transition of nucleic acid drug development into clinical application. | Zesen Ma Haiyang Tong Sijin Lin Li Zhou Demeng Sun Baoqing Li Changlin Tian Jiaru Chu | 2024 | Nano Research2024，17，4： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员