共查询到20条相似文献,搜索用时 0 毫秒
1.
Zhang H Wang G Ding Y Wang Z Barraclough R Rudland PS Fernig DG Rao Z 《Journal of molecular biology》2003,325(4):785-794
S100P is a small calcium-binding protein of the S100 EF-hand-containing family of proteins. Elevated levels of its mRNA are reported to be associated with the progression to hormone independence and metastasis of prostate cancer and to be associated with loss of senescence in human breast epithelial cells in vitro. The first structure of human recombinant S100P in calcium-bound form is now reported at 2.0A resolution by X-ray diffraction. A flexible linker connects the two EF-hand motifs. The protein exists as a homodimer formed by non-covalent interactions between large hydrophobic areas on monomeric S100P. Experiments with an optical biosensor to study binding parameters of the S100P monomer interaction showed that the association rate constant was faster in the presence of calcium than in their absence, whereas the dissociation rate constant was independent of calcium. The K(d) values were 64(+/-24)nM and 2.5(+/-0.8) microM in the presence and in the absence of calcium ions, respectively. Dimerization of S100P is demonstrated in vivo using the yeast two-hybrid system. The effect of mutation of specific amino acids suggests that dimerization in vivo can be affected by amino acids on the dimer interface and in the hydrophobic core. 相似文献
2.
Retinoic acid increases expression of the calcium-binding protein S100P in human gastric cancer cells 总被引:2,自引:0,他引:2
Retinoids mediate a wide spectrum of antitumor activities through induction of growth arrest, differentiation or apoptosis. To determine whether the effects of retinoids are mediated by specific gene activation or repression, one-day treatments of SC-M1 CL23 gastric cancer cells with vehicle alone or all-TRANS retinoic acid (tRA) (10 microM) were compared using differential display analysis. A 432-bp cDNA fragment from the tRA-treated cells was differentially amplified and its sequence analysis indicated homology with the calcium-binding protein S100P. Levels of S100P mRNA were increased 3.5-fold in SC-M1 CL23 gastric cancer cells treated with 10 microM tRA for 1 day, and the regulation was time- and concentration-dependent. Treatment with tRA (10 microM) also increased S100P mRNA levels in tRA-sensitive HtTA cells but not in inherent RA-resistant TMC-1 cells. However, the tRA-mediated increase in S100P expression was maintained in SC-M1/R cells that were established long-term in tRA-containing medium and had acquired partial RA resistance to tRA-induced growth suppression. In conclusion, tRA increases S100P expression, and the regulation remains intact in cells which develop acquired RA resistance. 相似文献
3.
Bovine Brain S100 Proteins: Separation and Characterization of a New S100 Protein Species 总被引:3,自引:3,他引:3
Three S100 protein species (S100a, S100b, S100a') have been purified from bovine brain using a modification of standard preparative methods. A higher yield for each protein was obtained at the last separation step. Characterization by urea/sodium dodecyl sulfate/polyacrylamide gel electrophoresis, UV absorption spectra, and fluorescence parameters provided evidence of a new tryptophan-containing S100 protein called S100a', which exhibits, as S100a and S100b, the properties of a Ca2+ binding protein. 相似文献
4.
Petri Kursula Gitte Tikkanen Veli-Pekka Lehto Morimitsu Nishikimi Anthony Heape 《Journal of neurochemistry》1999,73(4):1724-1732
The myelin-associated glycoprotein is a transmembrane cell adhesion molecule expressed by myelinating glial cells of the nervous system. So far, only protein kinases have been reported to interact with the cytoplasmic domains of the two isoforms of the myelin-associated glycoprotein. We report here the identification of the first nonkinase intracellular ligand for the large isoform of the myelin-associated glycoprotein as the S100beta protein. The interaction is dependent on the presence of calcium. We have also localized the S100beta-binding site in the cytoplasmic domain specific to the large myelin-associated glycoprotein isoform to a putative basic amphipathic alpha-helix. A synthetic peptide corresponding to this region bound to S100beta in a calcium-dependent manner with a stoichiometric ratio of 1:1 (K(D) approximately 7 microM). We suggest that the observed interaction may play a role in the regulation of the myelinating glial cell cytoskeleton and the divalent cation-dependent signal transduction events during myelin formation and maintenance. 相似文献
5.
《Cell calcium》2019
S100 proteins constitute a large subfamily of the EF-hand superfamily of calcium binding proteins. They possess one classical EF-hand Ca2+-binding domain and an atypical EF-hand domain. Most of the S100 proteins form stable symmetric homodimers. An analysis of literature data on S100 proteins showed that their physiological concentrations could be much lower than dissociation constants of their dimeric forms. It means that just monomeric forms of these proteins are important for their functioning. In the present work, thermal denaturation of apo-S100P protein monitored by intrinsic tyrosine fluorescence has been studied at various protein concentrations within the region from 0.04–10 μM. A transition from the dimeric to monomeric form results in a decrease in protein thermal stability shifting the mid-transition temperature from 85 to 75 °C. Monomeric S100P immobilized on the surface of a sensor chip of a surface plasmon resonance instrument forms calcium dependent 1 to 1 complexes with human interleukin-11 (equilibrium dissociation constant 1.2 nM). In contrast, immobilized interleukin-11 binds two molecules of dimeric S100P with dissociation constants of 32 nM and 288 nM. Since effective dissociation constant of dimeric S100P protein is very low (0.5 μM as evaluated from our data) the sensitivity of the existing physical methods does not allow carrying out a detailed study of S100P monomer properties. For this reason, we have used molecular dynamics methods to evaluate structural changes in S100P upon its transition from the dimeric to monomeric state. 80-ns molecular dynamics simulations of kinetics of formation of S100P, S100B and S100A11 monomers from the corresponding dimers have been carried out. It was found that during the transition from the homo-dimer to monomer form, the three S100 monomer structures undergo the following changes: (1) the helices in the four-helix bundles within each monomer rotate in order to shield the exposed non-polar residues; (2) almost all lost contacts at the dimer interface are substituted with equivalent and newly formed interactions inside each monomer, and new stabilizing interactions are formed; and (3) all monomers recreate functional hydrophobic cores. The results of the present study show that both dimeric and monomeric forms of S100 proteins can be functional. 相似文献
6.
The NMR assignments of backbone 1H, 13C,and 15N resonances for calcium-bound human S100B werecompleted via heteronuclear multidimensional NMR spectroscopic techniques.NOE correlations, amide exchange, 3JHNHcoupling constants, and CSI analysis were used to identify the secondarystructure for Ca-S100B. The protein is comprised of four helices (helix I,Glu2-;Arg20; helix II,Glu31-;Asn38; helix III,Gln50-;Thr59; helix IV,Phe70-;Phe87), three loops (loop I,Glu21-;His25; loop II,Glu39-;Glu49; loop III,Leu60-;Gly66), and two -strands(strand I, Lys26>-;Lys28; strand II,Glu67-;Asp69) which form a shortantiparallel -sheet. Helix IV is extended by approximately one turnwhen compared to the secondary structures of apo-rat [Drohat et al. (1996)Biochemistry, 35, 11577-;11588] and bovine S100B [Kilby et al. (1996)Structure, 4, 1041-;1052]. In addition, several residues outside thecalcium-binding loops in S100B undergo significant backbone chemical shiftchanges upon binding calcium which are not observed in the related proteincalbindin D9k. Together these observations support previoussite-directed mutagenesis, absorption spectroscopy, and cysteine chemicalreactivity experiments, suggesting that the C-terminus in Ca-S100B isimportant for interactions with other proteins. 相似文献
7.
Jan van Dieck Agnes M. Jaulent Trevor J. Rutherford Alan R. Fersht 《Journal of molecular biology》2009,394(5):922-9065
Proteins of the S100 family bind to the intrinsically disordered transactivation domain (TAD; residues 1-57) and C-terminus (residues 293-393) of the tumor suppressor p53. Both regions provide sites that are subject to posttranslational modifications, such as phosphorylation and acetylation, that can alter the affinity for interacting proteins such as p300 and MDM2. Here, we found that S100A1, S100A2, S100A4, S100A6, and S100B bound to two subdomains of the TAD (TAD1 and TAD2). Both subdomains were mandatory for high-affinity binding to S100 proteins. Phosphorylation of Ser and Thr residues increased the affinity for the p53 TAD. Conversely, acetylation and phosphorylation of the C-terminus of p53 decreased the affinity for S100A2 and S100B. In contrast, we found that nitrosylation of S100B caused a minor increase in binding to the p53 C-terminus, whereas binding to the TAD remained unaffected. As activation of p53 is usually accompanied by phosphorylation and acetylation at several sites, our results suggest that a shift in binding from the C-terminus in favor of the N-terminus occurs upon the modification of p53. We propose that binding to the p53 TAD might be involved in the stimulation of p53 activity by S100 proteins. 相似文献
8.
Parminder J.S. Vig 《Bioscience Hypotheses》2009,2(5):343-344
The autosomal dominant spinocerebellar ataxias (SCA) are a heterogeneous group of disorders that differ in the extent of neuropathological involvement of cerebellum, brainstem, and basal ganglia. Neuropsychiatric symptoms, such as depressive and memory symptoms, are common presenting symptoms in SCA patients. A mechanistic connection between different regions of the brain involved in major depression comes from the down regulation of glial function. We hypothesize that the impaired S100B signaling pathway is a common link between SCA and major depression, and that the onset of neuropsychiatric symptoms in patients with SCA are due to glial dysfunction in specific areas of the brain. Understanding of S100B dependent pathway will help develop new therapeutic strategies for treating cerebellar disorders and depression. 相似文献
9.
10.
Intra- and Interchain Disulfide Bond Generation in S100b Protein 总被引:1,自引:0,他引:1
Disulfide-bridged S100b protein formation, aircatalyzed and induced by thiol/disulfide exchange, was studied under various ionic conditions. As native, physiological disulfide-bridged proteins are obtained easily from their reduced counterparts under appropriate redox conditions, this work was performed to determine whether this was the case for disulfide-bridged S100b proteins, reported to have neurite extension activity. In nondenaturating native medium, no disulfide-bridged species could be generated from reduced proteins in any of the ion-induced conformations tested (no ions, Ca2+, Zn2+, or K+) under widely different redox conditions. Only mixed disulfides accumulated, in certain cases. In contrast, intrasubunit monomeric and intersubunit dimeric disulfide-bridged species were readily and efficiently generated under denaturating conditions. A brief characterization of these oxidized species suggested that they differed widely in structure from their reduced counterparts and that they probably did not bind Ca2+. Taken together, these data question the physiological relevance of these disulfide-bridged S100b protein species. 相似文献
11.
The three-dimensional solution structure of apo rabbit lung calcyclin has been refined to high resolution through the use of heteronuclear NMR spectroscopy and 13C,15N- enriched protein. Upon completing the assignment of virtually all of the 15N, 13C and 1H NMR resonances, the solution structure was determined from a combination of 2814 NOE- derived distance constraints, and 272 torsion angle constraints derived from scalar couplings. A large number of critical inter- subunit NOEs (386) were identified from 13C- select,13C-filtered NOESY experiments, providing a highly accurate dimer interface. The combination of distance geometry and restrained molecular dynamics calculations yielded structures with excellent agreement with the experimental data and high precision (rmsd from the mean for the backbone atoms in the eight helices: 0.33 Å). Calcyclin exhibits a symmetric dimeric fold of two identical 90 amino acid subunits, characteristic of the S100 subfamily of EF-hand Ca2+-binding proteins. The structure reveals a readily identified pair of putative sites for binding of Zn2+. In order to accurately determine the structural features that differentiate the various S100 proteins, distance difference matrices and contact maps were calculated for the NMR structural ensembles of apo calcyclin and rat and bovine S100B. These data show that the most significant variations among the structures are in the positioning of helix III and in loops, the regions with least sequence similarity. Inter-helical angles and distance differences for the proteins show that the positioning of helix III of calcyclin is most similar to that of bovine S100B, but that the helix interfaces are more closely packed in calcyclin than in either S100B structure. Surprisingly large differences were found in the positioning of helix III in the two S100B structures, despite there being only four non-identical residues, suggesting that one or both of the S100B structures requires further refinement. 相似文献
12.
S100A8 and S100A9 are calcium-binding proteins expressed in myeloid cells and are markers of numerous inflammatory diseases
in humans. S100A9 has been associated with dystrophic calcification in human atherosclerosis. Here we demonstrate S100A8 and
S100A9 expression in murine and human bone and cartilage cells. Only S100A8 was seen in preosteogenic cells whereas osteoblasts
had variable, but generally weak expression of both proteins. In keeping with their reported high-mRNA expression, S100A8
and S100A9 were prominent in osteoclasts. S100A8 was expressed in alkaline phosphatase-positive hypertrophic chondrocytes,
but not in proliferating chondrocytes within the growth plate where the cartilaginous matrix was calcifying. S100A9 was only
evident in the invading vascular osteogenic tissue penetrating the degenerating chondrocytic zone adjacent to the primary
spongiosa, where S100A8 was also expressed. Whilst, S100A8 has been shown to be associated with osteoblast differentiation,
both S100A8 and S100A9 may contribute to calcification of the cartilage matrix and its replacement with trabecular bone, and
to regulation of redox in bone resorption. 相似文献
13.
Characterization of the tissue-specific expression of the S100P gene which encodes an EF-hand Ca2+-binding protein* 总被引:2,自引:0,他引:2
S100 proteins are a calcium-binding protein family containing two EF-hand domains exclusively expressed in vertebrates and play roles in many cellular activities. Human S100P gene was first cloned as a 439 bp cDNA in placenta and it was found to be associated with human prostate cancer. Here we describe the cloning of the 1297 bp full-length cDNA, and the characterization of the tissue-specific expression of the human S100P gene. It is abundantly expressed in many tissues including placenta by Northern blot and RT-PCR analysis, unlike the expression pattern of other S100 family genes. 相似文献
14.
钙结合蛋白S100A14是S100家族中的新成员,其空间结构与功能尚未阐明。采用服务器PredictProtein对人S100A14进行二级结构预测,利用同源建模法构建S100A14(序列12-102)的空间结构模型,经PROCHECK评估模型的可靠性,并将所构建的单体模型进行分子对接,预测S100A14形成同源二聚体的可能性及模式。结果显示,S100A14与S100A13的蛋白序列一致性最高,其C-端Ca2+结合区存在多个变异,但Cu2+和Zn2+结合位点保守存在;helix I与helix IV较S100A13延伸长,而helix I、helix II和helix IV与S100A13的四个α螺旋一样具有两亲性的结构特征,并且在S100A13中扮演重要角色的W77在S100A14的helix IV(W85)中也保守存在。空间结构上,S100A14与S100A13具极大相似性;分子对接显示S100A14单体间可以通过疏水作用力形成"X-型螺旋束"同源二聚体。这些结构特征的分析将为S100A14的功能研究提供重要线索。 相似文献
15.
S100A4蛋白与肿瘤血管生成的研究进展 总被引:1,自引:0,他引:1
肿瘤血管生成是指肿瘤细胞诱导的微血管生长以及肿瘤中血液循环建立的过程。重要脏器的转移是恶性肿瘤致死的主要原因,而肿瘤生长、转移和复发都依赖于肿瘤血管生成.S100A4基因是近几年发现的一种具有促肿瘤作用的基因,该基因编码一种钙离子结合调节蛋白,通过与钙离子结合在肿瘤发生和发展中起重要作用。目前研究认为该蛋白在肿瘤的侵袭和转移中有促血管生成作用.本文主要就S100A4与肿瘤血管生成的有关研究进展加以综述。 相似文献
16.
James W. Cosgrove John J. Heikkila Alexander Marks Ian R. Brown 《Journal of neurochemistry》1983,40(3):806-813
Abstract: Free and membrane-bound polysomes were isolated from the cerebral hemispheres and cerebellum of the young adult rabbit. The two polysomal populations were translated in an mRNA-dependent cell-free system derived from rabbit reticulocytes. Analysis of the [35 S]methionine-labeled translation products on two-dimensional polyacrylamide gels indicated an efficient separation of the two classes of brain polysomes. The relative synthesis of S100 protein by free and membrane- bound polysomes was determined by direct immuno-precipitation of the cell-free translation products in the presence of detergents to reduce nonspecific trapping. Synthesis of S100 protein was found to be twofold greater on membrane-bound polysomes compared with free polysomes isolated from either the cerebral hemispheres or the cerebellum. In addition, the proportion of poly- (A+)mRNA coding for SlOO protein was also twofold greater in membrane-bound polysomes compared with free polysomes isolated from the cerebral hemispheres. These results indicate that the cytoplasmic S100 protein is synthesized predominantly on membrane-bound polysomes in the rabbit brain. We suggest that the nascent S100 polypeptide chain translation complex is attached to the rough endoplasmic reticulum by an ionic interaction involving a sequence of 13 basic amino acids in S100 protein. 相似文献
17.
Porcine S100A12 is a member of the S100 proteins, family of small acidic calcium-binding proteins characterized by the presence of two EF-hand motifs. These proteins are involved in many cellular events such as the regulation of protein phosphorylation, enzymatic activity, protein-protein interaction, Ca2+ homeostasis, inflammatory processes and intermediate filament polymerization. In addition, members of this family bind Zn2+ or Ca2+ with cooperative effect on binding. In this study, the gene sequence encoding porcine S100A12 was obtained by the synthetic gene approach using E. coli codon bias. Additionally, we report a thermodynamic study of the recombinant S100A12 using circular dichroism, fluorescence and isothermal titration calorimetry. The results of urea and temperature induced unfolding and refolding processes indicated a reversible two-state process. Also, the ANS fluorescence studies showed that in presence of divalent ions the protein exposes hydrophobic sites which could facilitate the interaction with other proteins and trigger the physiological responses. 相似文献
18.
Ribeiro L Andreazza AC Salvador M da Silveira TR Vieira S Nora DB Bosa C Di Napoli F Schaf DV Souza DO Portela LV Kapczinski F 《Neurochemical research》2007,32(9):1600-1603
Cirrhosis represents the terminal stage of a number of chronic liver diseases. Consequences include accumulation of toxic
metabolic wastes, reduced synthesis of key proteins, increased portal venous pressure, and portosystemic shunting. We conducted
a case-control study to assess the serum levels of S100B protein and parameters of oxidative stress, superoxide dismutase
(SOD), catalase (CAT) and oxidative stress measured by the thiobarbituric acid method (TBARS), in a group of 14 pediatric
patients with cirrhosis. No differences were found between groups in S100B protein levels. SOD activity and TBARS levels were
higher; and CAT activity was lower in the cirrhotic group. A negative correlation between S100B and TBARS in the case group
was found (r = −0.815, p = 0.001). Conclusions: This study didn’t indicate a possible role of S100B serum levels as marker of brain damage in cirrhotic children but suggest
a possible relation between astrocyte function and oxidative damage in cirrhotic children. 相似文献
19.
Joseph P. Zackular Walter J. Chazin Eric P. Skaar 《The Journal of biological chemistry》2015,290(31):18991-18998
The S100 family of EF-hand calcium (Ca2+)-binding proteins is essential for a wide range of cellular functions. During infection, certain S100 proteins act as damage-associated molecular patterns (DAMPs) and interact with pattern recognition receptors to modulate inflammatory responses. In addition, these inflammatory S100 proteins have potent antimicrobial properties and are essential components of the immune response to invading pathogens. In this review, we focus on S100 proteins that exhibit antimicrobial properties through the process of metal limitation, termed nutritional immunity, and discuss several recent advances in our understanding of S100 protein-mediated metal sequestration at the site of infection. 相似文献
20.
The hetero-oligomeric complex of the S100A8/S100A9 protein is extremely protease resistant 总被引:1,自引:0,他引:1
S100A8, S100A9 and S100A12 proteins are associated with inflammation and tissue remodelling, both processes known to be associated with high protease activity. Here, we report that homo-oligomeric forms of S100A8 and S100A9 are readily degraded by proteases, but that the preferred hetero-oligomeric S100A8/A9 complex displays a high resistance even against proteinase K degradation. S100A12 is not as protease resistant as the S100A8/A9 complex. Since specific functions have been assigned to the homo- and heterooligomeric forms of the S100A8 and A9 proteins, this finding may point to a post-translational level of regulation of the various functions of these proteins in inflammation and tissue remodelling. 相似文献