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PubMed1992

The DNA-binding defect observed in major histocompatibility complex class II regulatory mutants concerns only one member of a family of complexes binding to the X boxes of class II promoters.

The X box of major histocompatibility complex class II promoters is essential for proper expression of class II genes. Here we show that two distinct protein-DNA complexes (A and B), which exhibit similar binding characteristics and identical contact points on the X box, can be formed. This suggests the existence of a family of related X box-binding factors. Complex B (and not complex A) is specifically affected in primary combined immunodeficiency, a congenital defect in class II gene regulation. RFX1, the first X box-binding protein cloned, encodes a functionally relevant factor present in complex A and not in complex B as originally suspected. This report also illustrates the need for caution in correlating specific cloned proteins with nuclear factors identified by DNA-binding assays, particularly when dealing with families of related proteins.

Base Sequence↗

PubMed2000

The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes.

Transcriptional activation requires both access to DNA assembled as chromatin and functional contact with components of the basal transcription machinery. Using the hormone-bound vitamin D(3) receptor (VDR) ligand binding domain (LBD) as an affinity matrix, we previously identified a novel multisubunit coactivator complex, DRIP (VDR-interacting proteins), required for transcriptional activation by nuclear receptors and several other transcription factors. In this report, we characterize the nuclear receptor binding features of DRIP205, a key subunit of the DRIP complex, that interacts directly with VDR and thyroid hormone receptor in response to ligand and anchors the other DRIP subunits to the nuclear receptor LBD. In common with other nuclear receptor coactivators, DRIP205 interaction occurs through one of two LXXLL motifs and requires the receptor's AF-2 subdomain. Although the second motif of DRIP205 is required only for VDR binding in vitro, both motifs are used in the context of an retinoid X receptor-VDR heterodimer on DNA and in transactivation in vivo. We demonstrate that both endogenous p160 coactivators and DRIP complexes bind to the VDR LBD from nuclear extracts through similar sequence requirements, but they do so as distinct complexes. Moreover, in contrast to the p160 family of coactivators, the DRIP complex is devoid of any histone acetyltransferase activity. The results demonstrate that different coactivator complexes with distinct functions bind to the same transactivation region of nuclear receptors, suggesting that they are both required for transcription activation by nuclear receptors.

Amino Acid Sequence↗

PubMed2001

p53 Stimulates TFIID-TFIIA-promoter complex assembly, and p53-T antigen complex inhibits TATA binding protein-TATA interaction.

Simian virus 40 large T antigen has been shown to inhibit p53-mediated transcription once tethered to p53-responsive promoters through interaction with p53. In this study we report that p53 stimulates transcription by enhancing the recruitment of the basal transcription factors, TFIIA and TFIID, on the promoter (the DA complex) and by inducing a conformational change in the DA complex. Significantly, we have demonstrated that T antigen inhibits p53-mediated transcription by blocking this ability of p53. We investigated the mechanism for this inhibition and found that DA complex formation was resistant to T-antigen repression when the TFIID-DNA complex was formed prior to addition of p53-T antigen complex, indicating that the T antigen, once tethered to the promoter by p53, targets TFIID. Further, we have shown that the p53-T antigen complex prevents the TATA binding protein from binding to the TATA box. Thus, these data suggest a detailed mechanism by which p53 activates transcription and by which T antigen inhibits p53-mediated transcription.

Antigens, Polyomavirus Transforming↗

PubMed2004

Role for Nhp6, Gcn5, and the Swi/Snf complex in stimulating formation of the TATA-binding protein-TFIIA-DNA complex.

The TATA-binding protein (TBP), TFIIA, and TFIIB interact with promoter DNA to form a complex required for transcriptional initiation, and many transcriptional regulators function by either stimulating or inhibiting formation of this complex. We have recently identified TBP mutants that are viable in wild-type cells but lethal in the absence of the Nhp6 architectural transcription factor. Here we show that many of these TBP mutants were also lethal in strains with disruptions of either GCN5, encoding the histone acetyltransferase in the SAGA complex, or SWI2, encoding the catalytic subunit of the Swi/Snf chromatin remodeling complex. These synthetic lethalities could be suppressed by overexpression of TOA1 and TOA2, the genes encoding TFIIA. We also used TFIIA mutants that eliminated in vitro interactions with TBP. These viable TFIIA mutants were lethal in strains lacking Gcn5, Swi2, or Nhp6. These lethalities could be suppressed by overexpression of TBP or Nhp6, suggesting that these coactivators stimulate formation of the TBP-TFIIA-DNA complex. In vitro studies have previously shown that TBP binds very poorly to a TATA sequence within a nucleosome but that Swi/Snf stimulates binding of TBP and TFIIA. In vitro binding experiments presented here show that histone acetylation facilitates TBP binding to a nucleosomal binding site and that Nhp6 stimulates formation of a TBP-TFIIA-DNA complex. Consistent with the idea that Nhp6, Gcn5, and Swi/Snf have overlapping functions in vivo, nhp6a nhp6b gcn5 mutants had a severe growth defect, and mutations in both nhp6a nhp6b swi2 and gcn5 swi2 strains were lethal.

Acetylation↗

PubMed2005

The Enhancer of split and Achaete-Scute complexes of Drosophilids derived from simple ur-complexes preserved in mosquito and honeybee.

BACKGROUND: In Drosophila melanogaster the Enhancer of split-Complex [E(spl)-C] consists of seven highly related genes encoding basic helix-loop-helix (bHLH) repressors and intermingled, four genes that belong to the Bearded (Brd) family. Both gene classes are targets of the Notch signalling pathway. The Achaete-Scute-Complex [AS-C] comprises four genes encoding bHLH activators. The question arose how these complexes evolved with regard to gene number in the evolution of insects concentrating on Diptera and the Hymenoptera Apis mellifera. RESULTS: In Drosophilids both gene complexes are highly conserved, spanning roughly 40 million years of evolution. However, in species more diverged like Anopheles or Apis we find dramatic differences. Here, the E(spl)-C consists of one bHLH (mbeta) and one Brd family member (malpha) in a head to head arrangement. Interestingly in Apis but not in Anopheles, there are two more E(spl) bHLH like genes within 250 kb, which may reflect duplication events in the honeybee that occurred independently of that in Diptera. The AS-C may have arisen from a single sc/l'sc like gene which is well conserved in Apis and Anopheles and a second ase like gene that is highly diverged, however, located within 50 kb. CONCLUSION: E(spl)-C and AS-C presumably evolved by gene duplication to the nowadays complex composition in Drosophilids in order to govern the accurate expression patterns typical for these highly evolved insects. The ancestral ur-complexes, however, consisted most likely of just two genes: E(spl)-C contains one bHLH member of mbeta type and one Brd family member of malpha type and AS-C contains one sc/l'sc and a highly diverged ase like gene.

Amino Acid Sequence↗

PubMed1987

Mechanism of dexamethasone 21-mesylate antiglucocorticoid action: I. Receptor-antiglucocorticoid complexes do not competitively inhibit receptor-glucocorticoid complex activation of gene transcription in vivo.

The actions of dexamethasone 21-mesylate (DM) have been studied in two recently developed cultured murine cell lines containing approximately 200 copies of episomal minichromosome. This minichromosome contains the glucocorticoid regulatory element in the mouse mammary tumor virus long terminal repeat fused upstream of v-rasH sequences in a totally defined primary sequence environment. The levels of v-rasH mRNA were measured as an index of glucocorticoid regulated expression of this chimeric gene. In addition, expression of the endogenous single copy mouse metallothionein I (MT-I) gene was monitored simultaneously. DM was found to be an essentially pure antagonist of dexamethasone (dex)-stimulated expression of both the episomal chimeric gene and the endogenous MT-I gene. The covalent labeling efficiency by DM of glucocorticoid receptors in intact cells approached 100%, surpassing previously observed whole cell DM labeling efficiencies. These results strengthen the hypothesis that covalent complex formation is responsible for antiglucocorticoid action. The efficiency of whole cell nuclear binding of covalent receptor-DM complexes was found to be approximately 50% of that seen with receptor-dex complexes. Analyses of long terminal repeat initiated v-rasH mRNA and MT-I mRNA inductions by dex in cells previously exposed to a subsaturating concentration of DM indicated that receptor-DM complexes do not inhibit by a competitive mechanism the transcriptional activation of these glucocorticoid responsive genes by receptor-dex complexes. These results do not rule out the possibility, however, that covalent receptor-DM complexes may still bind to the biologically active nuclear sites. The implications of this result concerning the mechanism of DM irreversible antiglucocorticoid action are discussed.

Animals↗

PubMed1994

The bithorax complex is regulated by trithorax earlier during Drosophila embryogenesis than is the Antennapedia complex, correlating with a bithorax-like expression pattern of distinct early trithorax transcripts.

The trithorax gene is required throughout development to maintain expression of homeotic genes of the bithorax and Antennapedia complexes. We determined complete structures of maternal and zygotic alternatively spliced trithorax transcripts, and found that two RNA isoforms are expressed in a surprising manner in the early embryo. At syncytial blastoderm their expression is confined to the ventral region fated to become mesoderm. An additional broad domain of trithorax expression arises during cellularization and is quickly resolved into four pair-rule-like stripes in the posterior half of the embryo. This early expression pattern suggested the possibility that trithorax is involved in the very early regulation of homeotic genes expressed only in the posterior region of the embryo. Indeed, transcription of bithorax complex genes in the mesoderm and ectoderm is altered in strong trithorax mutants during germ band elongation, while the anteriorly expressed Antennapedia complex genes are affected only at late stages of embryonic development. In addition, in another mutant allele (trxE3), expression of bithorax complex genes is normal, while expression of Antennapedia complex genes is reduced. These results suggest that proper expression of genes in the two homeotic complexes is maintained by products of different trithorax RNAs at different times of embryogenesis.

Amino Acid Sequence↗

PubMed2006

Genetic and molecular interactions of the Erv41p-Erv46p complex involved in transport between the endoplasmic reticulum and Golgi complex.

Erv41p and Erv46p are integral membrane proteins conserved across species. They were originally identified as abundant constituents of COPII-coated vesicles, and form a complex which cycles between the endoplasmic reticulum and Golgi complex. Yeast strains lacking these proteins are viable but display subtle secretory phenotypes. In order to obtain information about possible biological roles of this protein complex in endoplasmic reticulum to Golgi transport, we employed the Synthetic Genetic Array approach to screen for synthetic genetic interactions with the erv46 null mutation. We identified synthetic interactions with vma12, vma21, vma22 and vps1 deletion mutations. The vma21Delta mutation exacerbates transport defects caused by the erv46Delta mutation. Unexpectedly, yeast strains lacking Vma21p fail to sort the endoplasmic reticulum to Golgi v-SNARE, Bos1p, efficiently into COPII vesicles, yet these vesicles are fully fusion competent. In addition, we set out to identify, by a biochemical approach, proteins interacting with the Erv41p-Erv46p complex. We report a strong interaction between the Erv41p-Erv46p complex and endoplasmic reticulum glucosidase II. Strains lacking a cycling Erv41p-Erv46p complex display a mild glycoprotein processing defect.

COP-Coated Vesicles↗

PubMed1990

Characterization of crystalline L-carnosine Zn(II) complex (Z-103), a novel anti-gastric ulcer agent: tautomeric change of imidazole moiety upon complexation.

A novel crystalline Zn(II) complex of L-carnosine was prepared and evaluated for inhibitory activity against gastric ulceration in rats. The complex was found to be much more active than various other Zn(II) compounds. It was characterized by means of infrared (IR) spectroscopy, solid-state carbon-13 (13C) and nitrogen-15 (15N) 1H-cross-polarization (CP) magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The spectroscopic data indicated that L-carnosine coordinates to Zn(II) as a quadridentate ligand. A comparison of the 13C-NMR signals of the imidazole carbons of the complex with those of several histidine derivatives revealed that a tautomeric change of imidazole moiety had occurred upon complexation. The binding mode of the complex was considered to be analogous to that of the corresponding Cu(II) complex.

Animals↗

PubMed1976

Human high denisty apolipoprotein A-I-lysolecithin-lecithin and sphingomyelin complexes. A method for high yield recombinations to lipoprotein complexes of reproducible stoichiometry.

High denisty apolipoprotein A-1 (apoLp A-I) has been prepared in a chromatographically and immunochemically homogeneous form. This apoprotein forms trimeric and tetrameric aggregates in aqueous solutions at higher concentrations. ApoLp A-I has been recombined in almost quantitative yield in the presence of lysolecithin with phosphatidylcholine and sphingomyelin to particles of reproducible stoichiometry. Lysolecithin is not required for the interactions of lecithin and sphingomyelin with the apoprotein A-I or for the stability of these complexes. Dialysis removes most of the lysolecithin without the loss of lecithin and sphingomyelin. ApoLp A-I-lecithin particles have a molecular weight of 200 000 and contain 50 molecules lecithin and 25 of lysolecithin. ApoLp A-I-sphingomyelin complexes contain 50 sphingomyelin and 13 lysolecithin molecules. The former particles show up as discs of 100 A diameter, and the latter particles are 250 A in diameter. Their thickness was estimated as 25 A in the apoLp A-I lecithin and 60 A in the apoLp A-I-sphingomyelin particles. ApoLp A-I and lysolecithin form complexes whose densities depend on the lysolecithin concentration. Lysolecithin enhances the binding of phosphatidylcholine to apoLP A-I, yielding lipoprotein complexes with decreasing density. The yield of apoLp A-I-sphingomyelin-lysolecithin complexes is proportional to the lysolecithin concentration. The ratio of apoLp A-I to sphingomyelin in all these complexes remains constant.

Apoproteins↗

PubMedDate not supplied

Microencapsulation of human insulin DEAE-dextran complex and the complex in liposomes by the emulsion non-solvent addition method.

Human insulin-DEAE (diethyl amino ethyl) dextran complex and human insulin DEAE-dextran complex in liposomes were encapsulated in cellulose acetate butyrate (CAB) microcapsules by the emulsion non-solvent addition method. The ratio of core-to-coat used was 1:1. The average diameters of the complex microcapsules and the complex liposome microcapsules were 239.5 +/- 77.5 and 182.9 +/- 52.2 microns respectively. In vitro dissolution studies of both types of microcapsules in simulated intestinal fluid at pH 7.2 showed a sustained release of the complex and the complex liposome microcapsules with t50 = 1.5 h and 4 h respectively. This study can be applied to the further development of oral formulations of human insulin liposomes for diabetic treatment.

Capsules↗

PubMed1991

[Recombination of micellar complexes of apolipoprotein A1--phosphatidylcholine in the presence of complex components].

Interaction of micellar complexes apolipoprotein A1--phosphatidyl choline (apoA1--DMPC and apoA1--EPC) with complex components: apoA1 (dansyl-A1) and phosphatydil cholines (DMPC, EPC and spin labelled PC) was studied in the absence of lipoproteins and plasma components. Recombination of the complexes (changes in complex sizes and stoichiometry) was shown to occur in the presence of the complex components. Interaction of lipid-free apoA1 with the complex is a fast process; incorporation of PC molecule takes place more slowly. This recombination is considered to be a kinetikally complicated process, the rate of recombination depending on PC exchange and interconversion.

Apolipoprotein A-I↗

PubMed2006

[Synthesis and characterization of phenyl-acetylmethylene sulfoxide complexes with light rare earth and fluorescence spectrum of Eu(III) complex].

Five solid complexes of phenyl-acetylmethylene sulfoxide(L) with light rare earth (La, Pr, Nd, Sm, Eu) were synthesized and characterized. Elemental analysis and molar conductivities show that the complexes have a composition of RE(ClO4)3 x L5 x 2H2O; two ClO4 anions coordinated with rare earth ions and the other did not. IR spectra suggested that the ligand coordinated with RE3+ by oxygen atom in sulfinyl group, and the oxygen atom in carbonyl group did not bond. The phosphorescence and 1H NMR and TG-DTA of the ligand and complexes were determind. Fluorescence spectra of Eu(III) complex with the sulfoxide indicated that the complex has no symmetrical center. All the complexes have good solubility.

English Abstract↗

PubMed1990

Inhibition of cofactor activity of protein S by a complex of protein S and C4b-binding protein. Evidence for inactive ternary complex formation between protein S, C4b-binding protein, and activated protein C.

To elucidate the mechanism by which C4b-binding protein inhibits the cofactor activity of protein S for anticoagulant-activated protein C, the interactions between protein S, activated protein C, and C4b-binding protein were studied using solid-phase enzyme immunoassays. Both activated protein C and C4b-binding protein bound to protein S fixed to microplate wells. C4b-binding protein did not inhibit the binding of activated protein C to protein S, nor did activated protein C inhibit the binding of C4b-binding protein to protein S. Activated protein C bound to a protein S-C4b-binding protein complex which was cross-linked with a chemical reagent as well as it bound to free protein S. Protein S-C4b-binding protein complex competitively inhibited activated protein C-binding to free protein S and also the cofactor activity of free protein S. Immunoblotting analysis showed ternary complex formation with protein S, C4b-binding protein, and activated protein C in the liquid phase by treatment with the cross-linking reagent. These findings suggest that the protein S-C4b-binding protein complex inhibits the cofactor activity of free protein S probably by inhibition of functionally active protein S-activated protein C complex formation by the apparent competitive formation of an inactive ternary complex with protein S, C4b-binding protein, and activated protein C.

Antibodies, Monoclonal↗

PubMed1989

The dnaB-dnaC replication protein complex of Escherichia coli. II. Role of the complex in mobilizing dnaB functions.

The dnaC protein of Escherichia coli, by forming a complex with the dnaB protein, facilitates the interactions with single-stranded DNA that enable dnaB to perform its ATPase, helicase, and priming functions. Within the dnaB-dnaC complex, dnaB appears to be inactive but becomes active upon the ATP-dependent release of dnaC from the complex. With adenosine 5'-(gamma-thio)triphosphate substituted for ATP, the dnaB-dnaC complex does not direct dnaB to its targeted actions. Excess dnaC inhibits dna beta actions and augments the ATP gamma S effects. In the dnaA protein-driven initiation of duplex chromosome replication, dnaB is introduced for its essential helicase role via the dnaB-dnaC complex. Similarly, when the dnaA protein interacts nonspecifically with single-stranded DNA, the dnaB-dnaC complex is essential to introduce dnaB for its role in primer formation by primase.

Adenosine Triphosphatases↗

PubMed1988

Comparison trial of iron succinylprotein complex or iron gluconate complex in the treatment of iron deficiency anemia.

Forty patients suffering from iron deficiency anemia were randomly assigned to receive iron succinylprotein complex (containing 80 mg of elemental iron daily) or iron gluconate complex (containing 125 mg of elemental iron daily) for two months. Improvement, as measured by hematological variables, was noted in both groups, iron succinylprotein complex being superior to iron gluconate complex on some measures. Side effects were reported by two of the 20 patients treated with iron succinylprotein complex and by ten of the 20 patients treated with iron gluconate complex.

Adult↗

PubMed1986

Complex of subtilisin BPN' with Streptomyces subtilisin inhibitor. Complex formation concomitant with change in reducibility of disulfide bonds in the inhibitor.

Structure of the complex of Streptomyces subtilisin inhibitor (SSI) with subtilisin BPN' was studied by examining the thermal denaturation and reducibility of disulfide bonds. The denaturation temperature of the complex was significantly higher than that of the enzyme. Two disulfide bonds localized in the inhibitor side were completely reduced in the complex, whereas only one of them was reduced in the free SSI. Gel filtration of the reduced complex solution showed clearly that the main products of reduction of the complex were two peptide fragments of SSI divided at the active site. The resistive disulfide bond in the complexed inhibitor became accessible as a result of a large conformational change due to splitting of the half-reduced inhibitor.

Bacterial Proteins↗

PubMed1985

Thymic lymphoid-stromal cell complexes in mice: in vitro assay and mechanism of the complex formation.

A quantitative assay was established to analyze in vitro thymic lymphoid-stromal cell complex formation. Major parameters of this assay were the number of thymic lymphocytes, incubation time, the age of the thymocyte donor, and the source and amount of serum used. The majority of complex-forming lymphocytes from normal young adult mice were found to have a blastlike morphology, indicating their possible origin from the subcapsular zone of the thymus. Changes of complex-forming cells during thymus development seemed to support this concept. The complex formation occurred in two steps: adherence of the lymphocytes to stromal cells and subsequent crawling of the lymphocytes under stromal cell cytoplasm. The first step was competitively inhibited by a serum activity and the second was noncompetitively inhibited by chemicals affecting cytoskeleton. In this assay, the behavior of normal complex-forming thymocytes was shown to be similar to that previously demonstrated for leukemia thymocytes with respect to morphology of the complex as well as the effects of certain inhibitors. This assay should provide the means both to analyze the nature of this cell interaction and to explore the relationship between thymocyte differentiation and a step in thymic leukemogenesis.

Animals↗