共查询到20条相似文献，搜索用时 15 毫秒
1.
Dimerization of human growth hormone by zinc 总被引：5，自引：0，他引：5
Size-exclusion chromatography and sedimentation equilbrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn(2+)-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn(2+)-hGH dimeric complex may be important for storage of hGH in secretory granules. 相似文献
2.
Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule 总被引：51，自引：0，他引：51
B C Cunningham M Ultsch A M De Vos M G Mulkerrin K R Clauser J A Wells 《Science (New York, N.Y.)》1991,254(5033):821-825
Human growth hormone (hGH) forms a 1:2 complex with the extracellular domain of its receptor-binding protein (hGHbp) as studied by crystallization, size exclusion chromatography, calorimetry, and a previously undescribed fluorescence quenching assay. These and other experiments with protein engineered variants of hGH have led to the identification of the binding determinants for two distinct but adjacent sites on hGH for the hGHbp, and the data indicated that there are two overlapping binding sites on the hGHbp for hGH. Furthermore, the binding of hGH to the hGHbp occurred sequentially; a first hGHbp molecule bound to site 1 on hGH and then a second hGHbp bound to site 2. Hormone-induced receptor dimerization is proposed to be relevant to the signal transduction mechanism for the hGH receptor and other related cytokine receptors. 相似文献
3.
Receptor and antibody epitopes in human growth hormone identified by homolog-scanning mutagenesis 总被引：21，自引：0，他引：21
A strategy, termed homolog-scanning mutagenesis, was used to identify the epitopes on human growth hormone (hGH) for binding to its cloned liver receptor and eight different monoclonal antibodies (Mab's). Segments of sequences (7 to 30 residues long) that were derived from homologous hormones known not to bind to the hGH receptor or Mab's, were systematically substituted throughout the hGH gene to produce a set of 17 chimeric hormones. Each Mab or receptor was categorized by a particular subset of mutant hormones was categorized by a particular subset of mutant hormones that disrupted binding. Each subset of the disruptive mutations mapped within close proximity on a three-dimensional model of hGH, even though the residues changed within each subset were usually distant in the primary sequence. The mapping analysis correctly predicted those Mab's which could or could not block binding of the receptor to hGH and further suggested (along with other data) that the folding of these chimeric hormones is like that of HGH. By this analysis, three discontinuous polypeptide determinants in hGH--the loop between residues 54 and 74, the central portion of helix 4 to the carboxyl terminus, and to a lesser extent the amino-terminal region of helix 1--modulate binding to the liver receptor. Homolog-scanning mutagenesis should be of general use in identifying sequences that cause functional variation among homologous proteins. 相似文献
4.
High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis 总被引：99，自引：0，他引：99
A strategy, called alanine-scanning mutagenesis, was used to identify specific side chains in human growth hormone (hGH) that strongly modulate binding to the hGH receptor cloned from human liver. Single alanine mutations (62 in total) were introduced at every residue contained within the three discontinuous segments of hGH (residues 2 to 19, 54 to 74, and 167 to 191) that have been implicated in receptor recognition. The alanine scan revealed a cluster of a dozen large side chains that when mutated to alanine each showed more than a four times lower binding affinity to the hGH receptor. Many of these residues that promote binding to the hGH receptor are altered in homologs of hGH (such as placental lactogens and prolactins) that do not bind tightly to the hGH receptor. The overall folding of these mutant proteins was indistinguishable from that of the wild-type hGH, as determined by strong cross-reactivities with seven different conformationally sensitive monoclonal antibodies. The alanine scan also identified at least one side chain, Glu174, that hindered binding because when it was mutated to alanine the receptor affinity increased by more than a factor of four. 相似文献
5.
Mutations introduced into human growth hormone (hGH) (Thr175 --> Gly-hGH) and the extracellular domain of the hGH receptor (Trp104 --> Gly-hGHbp) created a cavity at the protein-protein interface that resulted in binding affinity being reduced by a factor of 10(6). A small library of indole analogs was screened for small molecules that bind the cavity created by the mutations and restore binding affinity. The ligand 5-chloro-2-trichloromethylimidazole was found to increase the affinity of the mutant hormone for its receptor more than 1000-fold. Cell proliferation and JAK2 phosphorylation assays showed that the mutant hGH activates growth hormone signaling in the presence of added ligand. This approach may allow other protein-protein and protein-nucleic acid interactions to be switched on or off by the addition or depletion of exogenous small molecules. 相似文献
6.
采用荧光光谱法和紫外光谱法研究了5种二价金属离子与牛血清白蛋白（BSA）的相互作用,通过生物大分子猝灭反应机制和结合位点模型研究发现锌离子Zn2+,镍离子Ni2+,钴离子Co2+ 和钙离子Ca2+ 均可导致牛血清白蛋白内源荧光猝灭,Zn2+,Ni2+ 和Co2+ 离子半径处在正常范围,能有效进入牛血清白蛋白结合位点与牛血清白蛋白结合形成超分子配合物,使牛血清白蛋白的二级结构发生改变,主要表现为静态猝灭。Ca2+离子半径较大,受空间位阻影响不能有效进入结合位点对BSA二级结构影响较小,不能与BSA形成配合物,表现为动态猝灭;而Mg2+ 由于大的水合半径阻碍了Mg2+ 与牛血清白蛋白的有效碰撞,使电子或能量的转移受阻,从而导致Mg2+ 对牛血清白蛋白内源荧光无猝灭作用。图3表2参16 相似文献
7.
利用原子吸收光谱和常规生长量测定法,研究了木霉菌T23对7种微量元素Mn2+、Ca2+、Mg2+、Cu2+、Zn2+、Fe2+、Mo6+的吸收利用及7种微量元素对木霉菌T23生长的影响。结果表明:木霉菌T23对7种微量元素的吸收率存在明显差异,能够大量吸收Mg2+、Zn2+、Cu2+、Ca2+、Mn2+和Fe2+,基本不吸收Mo6+元素。在微量元素对木霉菌T23生长的影响方面,则表现为Ca2+、Mn2+、Zn2+可不同程度地促进木霉菌T23产孢,Cu2+、Mn2+、Mg2+、Ca2+、Zn2+在组合培养基中促进木霉菌T23菌丝生长,Mo6+抑制木霉菌T23的菌丝生长和产孢。 相似文献
8.
The Effect ofAdministration of Rutin on Plasma Levels of Estrogen,Prolactin, Growth Hormone and Gene Expression of Their Receptors in Mammary Glands in Ovariectomized Rats 
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下载免费PDF全文 GUO Xu-dong DIAO Qi-yu WANG Yue-ying TU Yan DENG Kai-dong WANG Xin-jian FU Tong YAN Gui-long 《农业科学学报》2012,12(10):1700-1706
The development of mammary glands, endocrine hormone concentrations and the gene expression of related receptors were measured in ovariectomized virgin rats after adminstration of an estrogen-like plant extract, rutin. Thirty-two ovariectomized virgin Wistar rats were randomly assigned to 4 treatments with 8 animals each: gastric infusion of 2 mL normal saline per unovariectomized rat per day (Sham), gastric infusion of 2 mL normal saline per ovariectomized rat per day (Ova), gastric infusion of 60 mg rutin kg-1 body weight (BW) per ovariectomized rat per day (Ova+Rut), or intramuscular injection of 60 μg estradiol kg-1 BW per ovariectomized rat weekly (Ova+Est). Samples of blood and mammary glands were harvested to determine the levels of estrogen (E2), prolactin (PRL) and growth hormone (GH), and the gene expression of estrogen receptors (ER), prolactin receptors (PRLR) and growth hormone receptors (GHR) with radioimmunoassy (RIA) and RT-PCR technology, respectively. The E2 concentration in plasma and gland tissues from the rats of Ovx+Rut or Ovx+Est was higher than that of Ovx (P<0.05), but the plasma E2 concentration from the rats of Ovx+Rut was lower than that of Sham (P<0.05). The order of the PRL concentration in plasma and gland tissues was Ovx 相似文献
9.
Tat protein from human immunodeficiency virus forms a metal-linked dimer 总被引：68，自引：0，他引：68
Tat, the transactivating protein from HIV, forms a metal-linked dimer with metal ions bridging cysteine-rich regions from each monomer. This novel arrangement is distinct from the "zinc finger" domain observed in other eukaryotic regulatory proteins. Ultraviolet absorption spectra show that Tat binds two Zn2+ or two Cd2+ ions per monomer, and electrophoresis of the Tat-metal complexes demonstrates that the protein forms metal-linked dimers. Partial proteolysis and circular dichroism spectra suggest that metal binding has its primary effects in the cysteine-rich region and relatively little effect on the folding of other regions. These results suggest new directions for biological studies and new approaches to drug design. 相似文献
10.
[目的]研究镧(La3+)、铈(Ce3+)、锌(Zn2+)对水稻根系的生理生化影响,探讨过量施用稀土的环境效应。[方法]以稀土元素镧(La3+)、铈(Ce3+)和兼具营养与毒性的重金属元素锌(Zn2+)为胁迫因子,采用组织培养法比较三者对水稻种子萌发及幼苗生长发育的影响。[结果]La3+、Ce3+和Zn2+对水稻种子萌发率影响很小,但对幼苗根、苗的生长具有显著的抑制作用,且在高浓度下稀土离子的抑制作用均大于Zn2+。水稻根可溶蛋白质含量随3种金属离子浓度的升高均呈先升后降的趋势,且La3+、Ce3+较Zn2+更为敏感;CAT和POD的活性随La3+、Ce3+和Zn2+浓度的增加逐渐上升,而SOD活性则先降后升;3种金属离子均能显著地刺激水稻根内MDA迅速积累。在高浓度下,La3+、Ce3+表现出比Zn2+更强的毒性。[结论]稀土元素La3+、Ce3+同重金属元素Zn2+对水稻的毒害机制相似。从长远来看,稀土有可能是一种新型的污染。 相似文献
11.
Requirement of nuclear prolactin for interleukin-2--stimulated proliferation of T lymphocytes 总被引：12，自引：0，他引：12
Prolactin (PRL) is necessary for the proliferation of cloned T lymphocytes in response to interleukin-2 (IL-2). Translocation of PRL into the nucleus occurs during IL-2--stimulated mitogenesis. Therefore, the function of intranuclear PRL in T cell proliferation was tested. Eukaryotic expression vectors were prepared to express wild-type PRL [PRL(WT)], PRL that lacks the signal sequence for translocation into the endoplasmic reticulum [PRL(ER-)], and chimeric PRL in which the signal peptide was replaced with the sequence that directs the nuclear translocation of the SV40 large T antigen [PRL(NT+)]. Expression of these constructs in a T cell line (Nb2) responsive to PRL and IL-2 resulted in localization of PRL in the extracellular milieu, cytoplasm, or nucleus, respectively. Stimulation with IL-2 alone resulted in a five- to tenfold increase in the incorporation of [3H]thymidine by cells expressing PRL(NT+) or PRL(WT) as compared to PRL(ER-) or the parental Nb2 cells. Only the PRL(NT+) clone proliferated continuously with IL-2 stimulation in the presence of antiserum to PRL. These results demonstrate that nuclear PRL is necessary for IL-2--stimulated proliferation and suggest that a peptide hormone can function in the nucleus without binding to its cell surface receptor. 相似文献
12.
[目的]综合筛选出对废水中Cu^2＋、Zn^2＋、Ni^2＋去除效果好的处理剂,为生产实践提供科学依据。[方法]用粉煤灰、煤渣、膨润土和沸石作为处理剂,分别对深圳某电镀厂废水进行吸附处理试验,检测滤液中Cu^2＋、Zn^2＋、Ni^2＋的浓度。[结果]膨润土对Cu^2＋、Zn^2＋、Ni^2＋3种离子的去除效果最好,平均去除率分别为98.89%、100%、99.75%。沸石对Cu^2＋、Zn^2＋、Ni^2＋3种离子的去除效果最差。粉煤灰、煤渣、沸石3种处理剂对Cu^2＋和Zn^2＋的去除效果都分别优于对Ni2＋的处理效果。[结论]粉煤灰对Cu^2＋和Zn^2＋的去除效果与膨润土的去除效果相近,粉煤灰可代替膨润土处理Cu^2＋和Zn^2＋,能降低80%的处理成本。 相似文献
13.
14.
YiiP is a membrane transporter that catalyzes Zn2+/H+ exchange across the inner membrane of Escherichia coli. Mammalian homologs of YiiP play critical roles in zinc homeostasis and cell signaling. Here, we report the x-ray structure of YiiP in complex with zinc at 3.8 angstrom resolution. YiiP is a homodimer held together in a parallel orientation through four Zn2+ ions at the interface of the cytoplasmic domains, whereas the two transmembrane domains swing out to yield a Y-shaped structure. In each protomer, the cytoplasmic domain adopts a metallochaperone-like protein fold; the transmembrane domain features a bundle of six transmembrane helices and a tetrahedral Zn2+ binding site located in a cavity that is open to both the membrane outer leaflet and the periplasm. 相似文献
15.
实验以EDTA和不同金属离子为效应物,果胶为反应底物,研究不同浓度的EDTA,Na+,K+,Ca2+,Cu2+,Zn2+,Mn2+,Fe2+,Fe3+,Ag+和Ba2+对多聚半乳糖醛酸酶(PG)催化活性的影响。结果表明,一定浓度的Cu2+,Zn2+,Mn2+,Fe2+和Fe3+对PG有激活作用,对PG产生最大激活作用的浓度分别为0.3mmol/L,0.4mmol/L,0.3mmol/L,0.3mmol/L和0.6mmol/L,EDTA,Ca2+,Ag+和Ba2+对PG有抑制作用,Na+和K+对PG活性没有影响。动力学研究表明,0.3mmol/LNa+和K+处理后,PG的Km和Vmax基本没有发生变化,2mmol/LEDTA和0.3mmol/LCa2+处理后,PG的Km和Vmax均下降,0.3mmol/LCu2+,Zn2+,Mn2+,Fe2+,Fe3+处理后,PG的Km和Vmax都上升,0.3mmol/LAg+和Ba2+处理后,PG的Km上升,Vmax下降。 相似文献
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【目的】探究重金属铜、铅、锌胁迫对药用植物黄芪植物种子萌发、生根、叶片叶绿素含量和DNA损伤的影响,为黄芪无公害栽培和药材基地环境评价提供理论依据。【方法】以内蒙特色药用植物黄芪为材料,设置不同浓度重金属（0～300 mg/L）单一和复合污染（Zn 200/Cu 200、Zn 200/Pb 200、Pb 200/Cu 200 mg/L）,观察黄芪生长状况及其叶片叶绿素含量的变化,并利用单细胞凝胶电泳技术检测黄芪DNA损伤情况。【结果】在0～100 mg/L时,Cu2+、Pb2+、Zn2+单一胁迫可促进黄芪种子萌发,大于100 mg/L时则抑制种子萌发。随着黄芪培养时间的延长和重金属离子处理浓度的升高, Pb2+处理的黄芪根生长受抑制逐渐增强,黄芪根长变短;Cu2+、Zn2+处理的黄芪根长呈先升高后降低的趋势,在不同时期内两者最长根长出现的处理浓度分别为60和100 mg/L。3种重金属Cu2+、Pb2+、Zn2+单一处理后,黄芪总叶绿素含量呈先增后降的变化趋势,当Cu2+处理浓度高于100 mg/L、Zn2+处理浓度高于200 mg/L、Pb2+处理浓度高于60 mg/L时,黄芪叶片叶绿素含量最高,随后不断降低。Cu/Zn、Zn/Pb复合胁迫,会降低彼此的毒害作用;Cu与Zn复合胁迫,对彼此毒害作用影响不大。随着重金属Zn2+、Pb2+、Zn2+浓度的增加,对黄芪DNA的伤害程度不断加大,Pb2+处理造成的损伤最大,Cu2+处理次之,Zn2+处理最小。【结论】一定含量的Pb2+、Cu2+、Zn2+对药用植物黄芪种子萌发、生根、叶绿素含量具有一定毒害作用,且随重金属浓度的增加,毒害程度加深。3种重金属离子的毒性大小排序为Pb2+＞Cu2+＞Zn2+。 相似文献
18.
烟草细胞凋亡过程中核酸酶活性研究 总被引：1，自引：1，他引：1
以烟草为材料 ,以 2 -甲基萘醌为诱导物 ,研究了植物细胞凋亡过程中核酸酶活性 ,结果表明 :2 -甲基萘醌诱导的烟草原生质体使鸡血红细胞发生了典型的凋亡现象 ,加入Zn2 +、EDTA、EGTA、AC -DEVD -CHO的样品无“DNAladder”出现 ;加入Ca2 +、Mg2 +后 ,“DNAladder”重新形成。 2 -甲基萘醌诱导的胞浆提取物和细胞核与只加细胞色素C诱导的胞浆提取物在电泳图上出现相同的蛋白条带 ,分子量约 36KD。从而表明 :烟草细胞凋亡过程中有特异核酸酶被激活 ,该核酸酶活性依赖于Ca2 +、Mg2 +,被Zn2 +、AC -DEVD -CHO抑制 ,该酶活性与caspase凋亡通路有关 相似文献
19.
Identification of a T3-associated gamma delta T cell receptor on Thy-1+ dendritic epidermal Cell lines 总被引：27，自引：0，他引：27
F Koning G Stingl W M Yokoyama H Yamada W L Maloy E Tschachler E M Shevach J E Coligan 《Science (New York, N.Y.)》1987,236(4803):834-837
The murine epidermis contains a subpopulation of bone marrow-derived lymphocytes that have a dendritic morphology and that express Thy-1 and T3 cell-surface antigens but not other markers (L3T4 or Lyt-2) characteristic of mature peripheral T lymphocytes. An alternative type of T cell receptor was earlier identified on a subpopulation of murine thymocytes with a similar phenotype (T3+, L3T4-, Lyt-2-), but not on peripheral murine T lymphocytes. Two independently derived Thy-1+, L3T4-, and Lyt-2- dendritic cell lines of epidermal origin that express a T3-associated disulfide-linked heterodimer composed of a 34-kilodalton gamma-chain and 46-kilodalton partner (the delta chain) have now been identified. Analysis of N-linked glycosylation revealed that this receptor is similar to that detected on thymocytes. These results demonstrate that Thy-1+ dendritic epidermal cell lines can express gamma delta T cell receptors in vitro and suggest that Thy-1+ dendritic epidermal cells express such receptors in vivo. The localization of these gamma delta T cell receptor-expressing cells in the epidermis may be of importance for understanding the function of these receptors. 相似文献
20.
Imura A Tsuji Y Murata M Maeda R Kubota K Iwano A Obuse C Togashi K Tominaga M Kita N Tomiyama K Iijima J Nabeshima Y Fujioka M Asato R Tanaka S Kojima K Ito J Nozaki K Hashimoto N Ito T Nishio T Uchiyama T Fujimori T Nabeshima Y 《Science (New York, N.Y.)》2007,316(5831):1615-1618
alpha-klotho was identified as a gene associated with premature aging-like phenotypes characterized by short lifespan. In mice, we found the molecular association of alpha-Klotho (alpha-Kl) and Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) and provide evidence for an increase of abundance of Na+,K+-ATPase at the plasma membrane. Low concentrations of extracellular free calcium ([Ca2+]e) rapidly induce regulated parathyroid hormone (PTH) secretion in an alpha-Kl- and Na+,K+-ATPase-dependent manner. The increased Na+ gradient created by Na+,K+-ATPase activity might drive the transepithelial transport of Ca2+ in cooperation with ion channels and transporters in the choroid plexus and the kidney. Our findings reveal fundamental roles of alpha-Kl in the regulation of calcium metabolism. 相似文献