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1.
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors 总被引:45,自引:0,他引:45
Brejc K van Dijk WJ Klaassen RV Schuurmans M van Der Oost J Smit AB Sixma TK 《Nature》2001,411(6835):269-276
Pentameric ligand gated ion-channels, or Cys-loop receptors, mediate rapid chemical transmission of signals. This superfamily of allosteric transmembrane proteins includes the nicotinic acetylcholine (nAChR), serotonin 5-HT3, gamma-aminobutyric-acid (GABAA and GABAC) and glycine receptors. Biochemical and electrophysiological information on the prototypic nAChRs is abundant but structural data at atomic resolution have been missing. Here we present the crystal structure of molluscan acetylcholine-binding protein (AChBP), a structural and functional homologue of the amino-terminal ligand-binding domain of an nAChR alpha-subunit. In the AChBP homopentamer, the protomers have an immunoglobulin-like topology. Ligand-binding sites are located at each of five subunit interfaces and contain residues contributed by biochemically determined 'loops' A to F. The subunit interfaces are highly variable within the ion-channel family, whereas the conserved residues stabilize the protomer fold. This AChBP structure is relevant for the development of drugs against, for example, Alzheimer's disease and nicotine addiction. 相似文献
2.
K C Gunter R N Germain R A Kroczek T Saito W M Yokoyama C Chan A Weiss E M Shevach 《Nature》1987,326(6112):505-507
In addition to monoclonal antibodies against the CD3 (T3)-T-cell antigen receptor (CD3/Ti) complex, several other monoclonals directed towards distinct cell surface structures on human (CD2 (T11) and Tp44) and murine (Thy-1, TAP, and Ly-6) T lymphocytes are capable of activating T cells. It has been proposed that such structures may function as alternative pathways of stimulation. To examine directly whether any relationship exists between Thy-1-dependent activation phenomena and T-cell activation mediated through the CD3/Ti complex, we have transfected several CD3/Ti- variants of the human T-cell line Jurkat with the murine Thy-1.2 gene. Our data indicate that in CD3/Ti-, Thy-1.2+ transfectants, monoclonal antibodies against Thy-1.2 can induce a rise in cytoplasmic free calcium ([Ca2+]i), but fail to stimulate interleukin-2 (IL-2) production. The only defect in these variant cell lines responsible for the inability to produce IL-2 in response to Thy-1 stimulation was in the expression of the CD3/Ti complex, because replacement of defective Ti alpha- or beta-chain genes reconstributed both surface expression of CD3/Ti and responsiveness to Thy-1 in the IL-2 production assay. 相似文献
3.
Resistance to infection and clearance of cell debris in mammals depend on the activation of the complement system, which is an important component of innate and adaptive immunity. Central to the complement system is the activated form of C3, called C3b, which attaches covalently to target surfaces to amplify complement response, label cells for phagocytosis and stimulate the adaptive immune response. C3b consists of 1,560 amino-acid residues and has 12 domains. It binds various proteins and receptors to effect its functions. However, it is not known how C3 changes its conformation into C3b and thereby exposes its many binding sites. Here we present the crystal structure at 4-A resolution of the activated complement protein C3b and describe the conformational rearrangements of the 12 domains that take place upon proteolytic activation. In the activated form the thioester is fully exposed for covalent attachment to target surfaces and is more than 85 A away from the buried site in native C3 (ref. 5). Marked domain rearrangements in the alpha-chain present an altered molecular surface, exposing hidden and cryptic sites that are consistent with known putative binding sites of factor B and several complement regulators. The structural data indicate that the large conformational changes in the proteolytic activation and regulation of C3 take place mainly in the first conversion step, from C3 to C3b. These insights are important for the development of strategies to treat immune disorders that involve complement-mediated inflammation. 相似文献
4.
R D Salter A M Norment B P Chen C Clayberger A M Krensky D R Littman P Parham 《Nature》1989,338(6213):345-347
Cytotoxic T lymphocytes (CTL) expressing the CD8 glycoprotein recognize peptide antigens presented by class I major histocompatibility complex (MHC) molecules. This correlation and the absence of CD8 polymorphism led to the hypothesis that CD8 binds to a conserved site of class I MHC molecules. Using a cell-cell binding assay we previously demonstrated specific interaction between human class I MHC (HLA-A,B,C) molecules and CD8. Subsequent analysis of the products of 17 HLA-A,B alleles revealed a natural polymorphism for CD8 binding in the human population. Two molecules, HLA-Aw68.1 and HLA-Aw68.2, which do not bind CD8, have a valine residue at position 245 whereas all other HLA-A,B,C molecules have alanine. Site-directed mutagenesis shows that this single substitution in the alpha 3 domain is responsible for the CD8 binding phenotype and also affects recognition by alloreactive and influenza-specific CTL. Our results indicate that CD8 binds to the alpha 3 domain of class I MHC molecules. 相似文献
5.
报道了可用于声光可调窄带滤光器的Ti∶LiNbO3单模条形波导结构的声光可调TE-TM模式转换器研制的初步结果,此模式转换器在1.5μm波段的带宽约6nm,在1.55μm得到70%的转换率,观察到了中心波长随驱动RF源频率变化的相应变化 相似文献
6.
R D Salter R J Benjamin P K Wesley S E Buxton T P Garrett C Clayberger A M Krensky A M Norment D R Littman P Parham 《Nature》1990,345(6270):41-46
Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 alpha-chain binds to the alpha 3 domain of HLA-A2.1. Three clusters of alpha 3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation. 相似文献
7.
Hepatitis C virus (HCV) is a human pathogen affecting nearly 3% of the world's population. Chronic infections can lead to cirrhosis and liver cancer. The RNA replication machine of HCV is a multi-subunit membrane-associated complex. The non-structural protein NS5A is an active component of HCV replicase, as well as a pivotal regulator of replication and a modulator of cellular processes ranging from innate immunity to dysregulated cell growth. NS5A is a large phosphoprotein (56-58 kDa) with an amphipathic alpha-helix at its amino terminus that promotes membrane association. After this helix region, NS5A is organized into three domains. The N-terminal domain (domain I) coordinates a single zinc atom per protein molecule. Mutations disrupting either the membrane anchor or zinc binding of NS5A are lethal for RNA replication. However, probing the role of NS5A in replication has been hampered by a lack of structural information about this multifunctional protein. Here we report the structure of NS5A domain I at 2.5-A resolution, which contains a novel fold, a new zinc-coordination motif and a disulphide bond. We use molecular surface analysis to suggest the location of protein-, RNA- and membrane-interaction sites. 相似文献
8.
用甲苯溶解试验,通过C60在MoO3/Al2O3催化剂上不同担载方式,研究了用N2、He及Air焙烧作用.结果表明:用N2焙烧时,先担载C60,后担载MoO3于Al2O3载体的样品中,MoO3、C60以及Al2O3之间相互作用最强,并生成了一种Mo-C60-O-Al新型复合物。 相似文献
9.
Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 A resolution. The structure reveals a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design. 相似文献
10.
采用配体取代法合成出C60Ni(PPh3)2,利用元素分析、红外光谱、光电子能谱对产物进行表征,研究了产物的热稳定性和氯化还原性能。 相似文献
11.
van Rossum DB Patterson RL Sharma S Barrow RK Kornberg M Gill DL Snyder SH 《Nature》2005,434(7029):99-104
Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cgamma1 (PLC-gamma1) binds to and regulates TRPC3 channels, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-gamma1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-gamma1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode. 相似文献
12.
Unusual intron in the immunoglobulin domain of the newly isolated murine CD4 (L3T4) gene 总被引:2,自引:0,他引:2
The T-cell surface glycoprotein, CD4, is expressed predominantly on helper T cells and is thought to play a major role in cell-cell interactions. Monoclonal antibodies against CD4 have been shown to block numerous T-cell functions; moreover, recent results suggest that the CD4 molecule may be involved in transmembrane signal transduction. The human CD4 glycoprotein has also been shown to form at least part of the receptor for the AIDS virus, HIV-1. Elucidation of the functions of CD4 will be facilitated by the ability to manipulate the protein by genetic means. Because the mouse system is well suited for a variety of functional studies, we have isolated, sequenced and expressed cDNA clones encoding the murine CD4 (L3T4) glycoprotein. Comparison of the mouse and human CD4 sequences reveals striking evolutionary conservation of the cytoplasmic domain, suggesting that this region is essential for CD4 function. In addition, both the human and mouse CD4 gene contain a large intron in the coding region of the V-like domain. As no other members of the immunoglobulin gene superfamily have been shown to contain similarly placed introns, this finding may have important implications regarding the evolution of this gene family in particular and of introns in general. 相似文献
13.
胡远芳 《湖北民族学院学报(自然科学版)》2004,22(4):15-16
合成了高氯酸镧与咪唑、DL-α-丙氨酸的配合物晶体.经傅立叶变换红外光谱、元素分析扣化学分析测定后确定其组成为[La(C3H7NO2)3(C3H4N2)(H2O)](ClO4)3用差示扫描量热法对配合物的热稳定性进行了研究,发现配合物有较高的热稳定性. 相似文献
14.
合成了富勒烯多金属配合物C60[CoCl(PPh)3)]n(n=2,4,6,8),采用元素分析、IR、XPS进行表征,该系列配合物为首次被合成。 相似文献
15.
MXene因其二维层状结构在锂离子电池负极材料研究领域展现出独特的优势,然而MXene片层间有很强的范德瓦尔斯力,导致了其发生堆叠,制约了其储锂性能表现.基于冷冻干燥技术制备了不同PVA含量的Ti3 C2 Tx MXene气凝胶,构筑了具有三维结构的电解液输运通道.借助X射线衍射仪(XRD)、扫描电子显微镜(SEM)、傅里叶变换红外光谱仪(FTIR)和共聚焦显微拉曼光谱仪(Raman)对气凝胶的微观结构与形貌进行了表征.储锂性能评估表明P400样品具有最高的比容量,其值为252.702 mA·h/g,在200圈充放电循环后,比容量依然能够保持在154.410 mA·h/g.发现随着PVA引入量增加使MXene交联行为增强,Ti3C2Tx MXene气凝胶空隙增大,有序度提高,进而优化了离子输运行为,提高了其储锂性能.该工作为基于二维MXene纳米片构筑三维结构电极提供了基础设计指导,为开发多孔结构电极提供了设计思路. 相似文献
16.
G W Booker A L Breeze A K Downing G Panayotou I Gout M D Waterfield I D Campbell 《Nature》1992,358(6388):684-687
Receptor protein-tyrosine kinases, through phosphorylation of specific tyrosine residues, generate high-affinity binding sites which direct assembly of multienzyme signalling complexes. Many of these signalling proteins, including phospholipase C gamma, GTPase-activating protein and phosphatidylinositol-3-OH kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and specificity to tyrosine-phosphorylated sequences. The critical role played by SH2 domains in signalling has been highlighted by recent studies showing that mutation of specific phosphorylation sites on the platelet-derived growth factor receptor impair its association with phosphatidylinositol-3-OH kinase, preventing growth factor-induced mitogenesis. Here we report the solution structure of an isolated SH2 domain from the 85K regulatory subunit of phosphatidylinositol-3-OH kinase, determined using multidimensional nuclear magnetic resonance spectroscopy. The structure is characterized by a central region of beta-sheet flanked by two alpha-helices, with a highly flexible loop close to functionally important residues previously identified by site-directed mutagenesis. 相似文献
17.
旨在探索不同介质的PCVD涂层对结构钢表面硬度及耐磨性的影响。实验采用两种不同的金属有机溶液((C3H7O)4Ti;(CH3)6SiN)对42CrMo钢进行表面处理。通过测量显微硬度及耐磨试验,得出以下结果:钛酸丙脂处理,其表面硬度及耐磨性均较好;而氮-硅烷处理,虽表面硬度较高,但耐磨性较差。这两种介质的表面处理都优于常规的离子渗氮 相似文献
18.
采用高温固相反应法首次合成了新型红色长余辉发光材料Gd2O2S:Eu3+,Si4+,Ti4+.用X射线粉末衍射(XRD)、扫描电镜(SEM)、分光光度计等对合成产物进行了分析与表征.结果表明:Gd2O2S:Eu3+,Si4+,Ti4+的晶体结构与Gd2O2S相同,为六方晶系.颗粒的形貌为类球形.Gd2O2S:Eu3+,Si4+,Ti4+的激发光谱呈250~400 nm宽带状,激发光谱主峰位于365 nm;发射光谱为线状光谱,归属于Eu3+的5DJ(J=0,1)→7FJ(K=0,1,2,4)跃迁.最强的发射峰为627 nm和617 nm,均属于5D0→7F2跃迁,且627 nm的发射峰明显远强于617nm,显示出纯正的红色发光;并且Si4+和Ti4+离子的共掺杂可显著延长样品Cd2O2S:Eu3+的余辉时间. 相似文献
19.
抗热震性能是结构陶瓷材料的重要性能之一.以抗热震断裂参数表征材料的抗热震性能,采用理论与实验相结合的方法,建立了基于抗热震性能的陶瓷复合材料的组分设计模型,并采用计算机辅助优化设计技术求得材料的最优组分.结果表明:当Ti(C,N)和SiC的体积含量分别为10.4%和27.1%时,该材料具有最高的抗热震性能,比纯氧化铝陶瓷提高约55%.在此基础上,利用热压技术制得一种SiC/Ti(C,N)/Al2O3复合陶瓷材料.将该材料制成切削刀具,并在切削实验中通过设计切削条件使得刀具主要承受热载荷和热应力的作用,从而发生热)中击破损.实验发现,SiC/Ti(C,N)/Al2O3复合陶瓷刀具切削淬火钢时的抗热)中击破损性能较纯Al2O3陶瓷提高约62-68%,与抗热震性能设计的理论预测基本吻合.这表明,该设计方法是可行的. 相似文献
20.
半封闭一步热解法制备层状类石墨相C3N4及其性能表征 总被引:1,自引:0,他引:1
在半封闭系统中一步热解三聚氰胺,采用X射线衍射(XRD)、透射电子显微镜(TEM)、化学元素分析(EA)、傅里叶红外光谱(FTIR)和X射线光电子能谱(XPS)分析热解产物的结构和形貌,并用热重分析(TG)和荧光分析(PL)研究了产物的热稳定性和荧光性质.XRD分析表明随着热解温度的提高,产物由Melem逐步转变为石墨相结构;FTIR和XPS分析结果表明,产物主要由含有大量sp2C-N双键和sp3C-N单键的碳氮结构组成;TEM照片显示产物具有多层结构.研究结果显示,当热解温度达到650℃时,可以获得碳氮量比为O.738的类石墨相结构C3N4.所制备的C3N4起始热分解温度达到700℃,在460 nm具有较大半峰宽的荧光吸收峰.该文研究为大规模制备类石墨相C3N4提供了一种新方法. 相似文献