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Results for “Multiprotein Complexes”

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PubMed2001

The maize WD-repeat gene ZmRbAp1 encodes a member of the MSI/RbAp sub-family and is differentially expressed during endosperm development.

Members of the MSI/RbAp sub-family of WD-repeat proteins are widespread in eukaryotic organisms and form part of multiprotein complexes that are involved in various biological pathways, including chromatin assembly, regulation of gene transcription, and cell division. In this study we report the isolation and characterization of a cDNA sequence from Zea mays, which encodes an RbAp-like protein (ZmRbAp1) that binds acetylated histones H3 and H4 and suppresses mutations that have a negative effect on the Ras/cAMP pathway in yeast. The ZmRbAp genes form a gene family and are expressed in different tissues of Z. mays L. plants. Determination of its expression pattern during maize seed development revealed that ZmRbAp transcripts are abundant during the initial stages of endosperm formation. In addition, the transcripts are specifically localized in shoot apical meristem and leaf primordia of the embryo. A possible role for the ZmRbAp genes in early endosperm differentiation and plant development is discussed.

Acetylation↗

PubMed1999

Two single nucleotide polymorphisms of the hSNF5/INI1 gene.

We found two single nucleotide polymorphisms at the hSNF5/INI1 gene located on 22q11.2, encoding a member of the chromatin-remodelling SWI/SNF multiprotein complexes. A guanine/adenine polymorphism at codon 299 in exon 7, and another guanine/adenine polymorphism at 39 bp upstream of exon 9 were identified. As the gene was recently identified as a tumor suppressor gene for malignant rhabdoid tumor, this polymorphism may be useful for the genetic study of susceptibility for human malignancies of various tissue origins.

Adenine↗

PubMed1992

Estrogen receptor-induced bending of the Xenopus vitellogenin A2 gene hormone response element.

DNA bending is increasingly proposed as an essential step for the establishment of the multiprotein complexes required for transcription initiation. Polyamines and metallic cations, known to promote DNA-bending, enhance the binding of purified estrogen receptor (ER) to the estrogen response element (ERE) of the Xenopus vitellogenin A2 gene. Using both circular permutation electrophoretic mobility and cyclization assays, we provide evidence that ER bends the DNA at the estrogen response element. The same bending occurs as a result of estrogen receptor protein binding independently of its conformational changes induced by hormone or anti-hormone. We suggest a role of the observed DNA bending in estrogen-regulated transcription.

Animals↗

PubMed1993

Liver-enriched HNF-3 alpha and ubiquitous factors interact with the human transferrin gene enhancer.

The human transferrin gene enhancer is organized in two domains. Domain A contains a single enhanson designated Ia. Domain B contains four enhansons named Ib, II, III and IV. We demonstrate here that the liver-enriched transcription factor HNF-3 alpha interacts with enhanson Ia and that enhansons Ib and IV are binding sites for members of the NF1 family. In addition, enhansons II and III seem to be respectively the targets for the AP4 protein and for EIII, a factor not yet completely identified. Analysis of mutated enhancer regions establishes that each enhanson is required for full enhancer activity and that the proteins binding to enhansons II, III and IV may interact within a multiprotein complex. This enhancer region presents no activity in the Sertoli cells of testis, where transferrin is also synthesized. We demonstrate that in Sertoli cells, the members of the HNF-3 family are not expressed; this fact may account for the inactivity of the enhancer in these cells.

Base Sequence↗

PubMed1993

Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators.

The general transcription factor TFIID is a multiprotein complex containing the TATA-binding protein and several associated factors (TAFs), some of which may function as coactivators that are essential for activated, but not basal, transcription. Here we describe the isolation and characterization of the first gene encoding a TAF protein. The deduced amino acid sequence of TAF110 revealed the presence of several glutamine- and serine/threonine-rich regions reminiscent of the protein-protein interaction domains of the regulatory transcription factor Sp1 that are involved in transcription activation and multimerization. In both Drosophila cells and yeast, TAF110 specifically interacts with the glutamine-rich activation domains of Sp1. Moreover, purified Sp1 selectively binds recombinant TAF110 in vitro. These findings taken together suggest that TAF110 may function as a coactivator by serving as a site of protein-protein contact between activators like Sp1 and the TFIID complex.

Amino Acid Sequence↗

PubMed1995

Phage T4 homologous strand exchange: a DNA helicase, not the strand transferase, drives polar branch migration.

Homologous strand exchange is a central step in general genetic recombination. A multiprotein complex composed of five purified bacteriophage T4 proteins (the products of the uvsX, uvsY, 32, 41, and 59 genes) that mediates strand exchange under physiologically relevant conditions has been reconstituted. One of these proteins, the product of the uvsY gene, is required for homologous pairing but strongly inhibits branch migration catalyzed by UvsX protein, the phage RecA analog. Branch migration is completely dependent on the gene 41 protein, a DNA helicase that also functions in phage replication. The helicase is delivered to the strand exchange complex by the gene 59 accessory protein in a strand-specific fashion through direct interactions between the gene 59 and gene 32 proteins. These data suggest that strand transferases such as UvsX protein are essential for homologous pairing in vivo, but that a DNA helicase drives polar branch migration.

Bacteriophage T4↗

PubMed1995

ISWI, a member of the SWI2/SNF2 ATPase family, encodes the 140 kDa subunit of the nucleosome remodeling factor.

The generation of an accessible heat shock promoter in chromatin in vitro requires the concerted action of the GAGA transcription factor and NURF, an ATP-dependent nucleosome remodeling factor. NURF is composed of four subunits and is biochemically distinct from the SWI2/SNF2 multiprotein complex, a transcriptional activator that also appears to alter nucleosome structure. We have obtained protein microsequence and immunological evidence identifying the 140 kDa subunit of NURF as ISWI, previously of unknown function but highly related to SWI2/SNF2 only in the ATPase domain. The ISWI protein is localized to the cell nucleus and is expressed throughout Drosophila development at levels as high as 100,000 molecules/cell. The convergence of biochemical and genetic studies on ISWI and SWI2/SNF2 underscores these ATPases and their close relatives as key components of independent systems for chromatin remodeling.

Adenosine Triphosphatases↗

PubMed1996

Effects of Mg2+ and denaturants on the unfolding pattern of DNA-T--a replication protein of E. coli.

Escherichia coli-DNA-T protein is a key component of a multiprotein complex called the primosome which is involved in the initiation of DNA replication. The thermal and urea induced unfolding transition of this protein in the presence and absence of Mg2+ was studied using circular dichroism (CD) and fluorescence spectroscopy as probes. Quenching of the intrinsic fluorescence of DNA-T was observed in the thermal unfolding while formation of a hyperfluorescent form of the protein was found in the urea induced unfolding process. The CD studies showed a monophasic transition curve for thermal unfolding in the presence and absence of Mg2+. Biphasic curves indicative of the formation of intermediates was observed in the urea induced unfolding. The results suggest that the pathways of unfolding of thermal- and urea-induced transitions are different. MgCl2, which affects the conformation of the protein and stabilises the secondary structure, also affects the unfolding pattern.

Bacterial Proteins↗

PubMed1991

The regulation of adenylyl cyclase by receptor-operated G proteins.

The receptor regulated adenylyl cyclase system is a multiprotein complex which is a member of the family of the receptor-effector systems whose signal is transduced by heterotrimeric GTP-binding proteins. The system consists of stimulatory and inhibitory receptors (Rs and Ri), stimulatory and inhibitory G proteins (Gs and Gi) and the adenylyl cyclase enzyme (C). While quite specific in situ, receptors (stimulatory or inhibitory) from one source can activate the appropriate G protein from other cell types or species which in turn can act on C from other sources. Studies with chimeric proteins have shown that the various specificities (stimulatory or inhibitory) can be mapped to defined domains in both receptors and G proteins. The mechanism by which the heterotrimeric G proteins couple to the stimulatory and inhibitory signals is discussed in detail. Specifically, the data supporting collision coupling vs the shuttle mechanism is reviewed, as well as the role of beta gamma subunits in both the stimulatory and inhibitory signals.

Adenylyl Cyclases↗

PubMed1994

Protein fluorescence, dynamics and function: exploration of analogy between electronically excited and biocatalytic transition states.

With the advent and development of time-resolved spectroscopic techniques and substantial progress in understanding of photophysical and photochemical phenomena, a new goal may be achieved: modeling of biochemical reaction or its elementary step by a photochemical event occurring within the probe, bound to a protein molecule. The probe may be located in a well-determined site of the protein matrix and report on the modulation of the reaction rate by the matrix and by the surrounding solvent, or by interactions in multiprotein complexes and in biomembranes. The advantages of this approach are obvious: in contrast to ordinary biochemical reaction, the excited-state reaction may be started by a short light pulse, and its kinetics may be observed directly with high resolution in time. In addition, if the reaction rate is influenced by the dynamics of the protein matrix, these dynamics may be studied simultaneously with the reaction, by using the same or a similar probe and within the same time range. In this review, the prospects for application of probes exhibiting electron transfer, proton transfer, molecular rotations and isomerizations are presented and discussed. The general problem of photochemical modeling of biochemical reactions is discussed. This modeling may result in deeper understanding of enzyme catalyzed reaction mechanisms.

Fluorescent Dyes↗

PubMed1996

Mechanisms of transcriptional activation in vivo: two steps forward.

Transcriptional activation involves the regulated assembly of multiprotein complexes on promoter DNA in the context of the repressive effects of chromatin. How do activators orchestrate this complicated phenomenon in vivo? Recent genetic and biochemical advancements suggest that activator-dependent formation of the transcription machinery on the promoter involves at least two steps. First, the activator facilitates the recruitment of TFIID to the TATA element of the promoter. TFIID binding is then followed by the recruitment of the remainder of the transcriptional apparatus in the form of the RNA polymerase II holoenzyme.

Chromatin↗

PubMed1993

Promoter resurrection by activators--a minireview.

Frequently, in nature, defective promoters can be resurrected by activator proteins in response to cellular demands. The activators bind to nearby DNA sites for action. Various protein-protein and DNA-protein contacts involving activators, RNA polymerase, and different segments of DNA in and around a defective promoter form a DNA-multiprotein complex (cage) which enhances transcription.

DNA↗

PubMed1994

The SNF/SWI family of global transcriptional activators.

The yeast SNF/SWI proteins have a global role in transcriptional activation. This set of five proteins assists many gene-specific activators, most likely by altering chromatin structure to relieve repression. Recent work shows that the SNF/SWI proteins function together in a multiprotein complex and that SNF2 has DNA-dependent ATPase activity. SNF/SWI homologs have now been identified in Drosophila, mice and humans, suggesting a conserved role in transcriptional activation.

Animals↗

PubMed1995

The proliferation of MAP kinase signaling pathways in yeast.

Mitogen-activated protein kinases function in at least five, physiologically distinct, signaling pathways in yeast. These include pathways that mediate response to mating pheromone, pseudohyphal development and invasive growth, cell integrity, sporulation, and response to high extracellular osmolarity. These kinases and their upstream activating kinases comprise signaling modules that, in at least some cases, exist as multiprotein complexes. Studies during the past year have revealed that the Ste5 protein of the mating pheromone response pathway serves as a scaffold to promote interactions among the protein kinases in this pathway, and to prevent their interaction with kinases of other modules.

Enzyme Activation↗

PubMed1992

Blotting and band-shifting: techniques for studying protein-protein interactions.

The type II cAMP-dependent protein kinase (PKA) is localized in certain cellular compartments through association with specific A-kinase anchoring proteins (AKAPs). A variety of blotting and electrophoresis techniques have been developed to study the protein-protein interactions that occur between the regulatory (R) subunit of PKA and AKAPs. These methods have also been used for a variety of purposes such as detecting calmodulin-binding proteins, comparing wild-type- and mutant-form binding affinities and estimating the molecular weight of multiprotein complexes.

Animals↗

PubMed1995

TBP binding to the TATA box induces a specific downstream unwinding site that is targeted by pluramycin.

BACKGROUND: The TATA-binding protein (TBP) is one of the major components of the human TFIID multiprotein complex. It is important in directing the initiation of RNA transcription at a site immediately downstream of the TATA sequence (TATA box) found in many eukaryotic promoters. The crystal structure of TBP complexed with an oligonucleotide containing the TATA box revealed a protein with an approximate two-fold symmetry which apparently has symmetrical interactions with DNA. It is not known how an asymmetric effect involving downstream activation can be produced by an apparent symmetric complex. We set out to examine the state of DNA in the TBP-DNA complex using pluramycin, a small molecular weight probe of DNA accessibility. RESULTS: Binding of TBP to the TATA box facilitates intercalation of pluramycin at a defined site immediately downstream of the TATA sequence through an apparent transient unwinding of the DNA. Pluramycin adducts are detected by the production of DNA strand breakage products upon heating. Incubation of pluramycin with the TBP-DNA complex facilitates the trapping of the specific complex by intercalation. Gel mobility shift and circularization assays reveal that the binding of pluramycin on the 3'-side of the TATA box region considerably stabilizes the TBP-DNA complex. CONCLUSIONS: We propose that the TBP-DNA-pluramycin ternary complex is a 'specific' binding mode in which TBP and pluramycin make compensatory alterations in DNA, accounting for the improved stability of the ternary complex. We also propose a model of the ternary complex that explains the observed asymmetric effect of TBP binding to the TATA box.

Aminoglycosides↗

PubMed2026

Histone deacetylases: From acetylation homeostasis to oncogenic and neurodegenerative disorders.

Histone deacetylases (HDACs) are central regulators of acetylation homeostasis, governing chromatin architecture, transcriptional dynamics, and diverse cellular processes through reversible lysine deacetylation. Dysregulation of HDAC activity disrupts epigenetic balance and is strongly implicated in oncogenic transformation and the progression of neurodegenerative disorders. This chapter provides a comprehensive overview of HDAC biology with a particular emphasis on experimental and analytical methodologies used to investigate their function. We describe the structural and functional diversity of HDAC classes and their roles in multiprotein complexes that regulate gene expression and cellular signaling. A major focus is placed on screening-compatible and mechanistic assays, including fluorometric, colorimetric, radiometric, fluorescence polarization, TR-FRET, AlphaScreen/AlphaLISA, and differential scanning fluorimetry approaches for quantitative measurement of enzymatic activity and inhibitor profiling. In addition, advanced methodologies such as mass spectrometry-based acetylome analysis, chromatin immunoprecipitation sequencing (ChIP-seq), recombinant enzyme assays, and cell-based reporter systems are discussed in the context of functional genomics and drug discovery. The integration of high-throughput screening, structural biology, and multi-omics strategies is highlighted as essential for dissecting HDAC-mediated regulatory networks. Collectively, this chapter serves as a methodological framework for studying HDAC function and developing targeted epigenetic therapies in cancer and neurodegenerative diseases.

Histone Deacetylases↗

PubMed2006

Tight junction modulation and its relationship to drug delivery.

In order for therapeutic agents to exert their pharmacological effects, they have to cross the biological membranes into the systemic circulation and reach the site of action. Drugs cross the membranes by one of two pathways; paracellular or transcellular. Most drugs are transported transcellularly depending on their physiocochemical properties, however the paracellular route is usually the main route of absorption for hydrophilic drugs (proteins, peptides, etc.). The paracellular pathway is governed by the tight junctions (TJs). The modulation of the TJs by absorption enhancers for paracellular drug transport enhancement and hence drug delivery improvement has been hampered for so many years by lack of comprehensive understanding of the structure and function of the TJs. The TJs are a multiple unit structure composed of multiprotein complex that affiliates with the underlying apical actomyosin ring. TJ proteins identified include transmembrane proteins; occludin and claudin, and cytoplasmic plaque proteins; ZO-1, ZO-2, ZO-3, cingulin, and 7H6. Among the new absorption enhancers that evolved in the past few years is Zonula Occludens toxin, Zot. In vivo and in vitro studies have shown that Zot and its biologically active fragment DeltaG could be effectively used to increase the transport/absorption of paracellular markers and low bioavailable drugs across the intestinal epithelium. Above all, the transient opening of the TJs by Zot suggests that it could be used as a novel approach for the safe drug delivery of therapeutic agents.

Animals↗