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At least 181 records · Page 10Linked to original sources
PubMed1988

Integration host factor interacts with the DNA replication enhancer of filamentous phage f1.

We present data which show that the Escherichia coli integration host factor (IHF) is an activator of phage f1 DNA replication. Phage f1 poorly infects bacterial strains lacking IHF because IHF is required for efficient expression of F-pili, the receptor for f1 phage. However, when F- strains are transfected with f1 DNA the phage replicates in IHF mutants (himA, himD, or himA himD) at a rate of only 3% of that in wild-type bacteria. A plasmid dependent on the f1 replicon fails to transform IHF mutants. By gel retardation analysis, we show that IHF specifically binds to the origin of replication. DNase I "footprinting" experiments demonstrate that IHF binds to multiple sites within the replication enhancer sequence, a cis-acting, A + T-rich sequence that potentiates f1 DNA replication. Moreover, the effect of IHF mutation on f1 growth is suppressed by initiator protein (f1 gene II) mutations that restore efficient replication from origins that lack a functional replication enhancer sequence. This genetic evidence supports the conclusion that the replication enhancer sequence is the site of action of IHF.

Bacterial Proteins↗
PubMed2003

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

Algorithms↗
PubMed2002

Integration host factor interactions with Neisseria gene sequences: correlation between predicted binding sites and in vitro binding of Neisseria -derived IHF protein.

Putative integration host factor (IHF) binding sites are frequently being identified in Neisseria gene sequences on the basis of similarity to a degenerate Escherichia coli -derived consensus binding sequence. In this report, three different Neisseria genetic systems that contain predicted IHF binding sites were assessed for IHF binding through gel retardation analysis. The results show a positive correlation between the identification of a predicted Neisseria IHF binding site and in vitro binding of Neisseria -derived IHF protein.

Base Sequence↗
PubMed1991

Genetic analysis of Escherichia coli integration host factor interactions with its bacteriophage lambda H' recognition site.

The bacteriophage P22-based challenge phage system was used to study the binding of integration host factor (IHF) to its H' recognition site in the attP region of bacteriophage lambda. We constructed challenge phages that carried H' inserts in both orientations within the P22 Pant promoter, which is required for antirepressor synthesis. We found that IHF repressed expression of Pant from either challenge phage when expressed from an inducible Ptac promoter on a plasmid vector. Mutants containing changes in the H' inserts that decrease or eliminate IHF binding were isolated by selecting challenge phages that could synthesize antirepressor in the presence of IHF. Sequence analysis of 31 mutants showed that most changes were base pair substitutions within the H' insert. Approximately one-half of the mutants contained substitutions that changed base pairs that are part of the IHF consensus binding site; mutants were isolated that contained substitutions at six of the nine base pairs of the consensus site. Other mutants contained changes at base pairs between the two subdeterminants of the H' site, at positions that are not specified in the consensus sequence, and in the dA + dT-rich region that flanks the consensus region of the site. Taken together, these results show that single-base-pair changes at positions outside of the proposed consensus bases can weaken or drastically disrupt IHF binding to the mutated site.

Bacterial Proteins↗
PubMed1994

Stabilization of platelet-fibrinogen interactions is an integral property of the glycoprotein IIb-IIIa complex.

Fibrinogen binding to platelets is multiphasic and culminates in the stabilization of platelet-fibrinogen interactions characterized by the resistance of bound fibrinogen to dissociation by ethylenediaminetetraacetic acid (EDTA) or excess unlabeled fibrinogen. Controversy exists, however, with regard to the exclusive role of the glycoprotein IIb-IIIa (GPIIb-IIIa) complex in this process. Thus the reversibility of fibrinogen binding to purified GPIIb-IIIa and GPIIb-IIIa activated by a monoclonal antibody (D3) on otherwise resting platelets was examined. GPIIb-IIIa was isolated by affinity chromatography on concanavalin A followed by gel filtration on Sephacryl S-300 and immobilized directly on plastic microtiter wells or immunocaptured by immobilized anti-GPIIb or GPIIIa antibodies. The extent of GPIIb-IIIa deposition, 0.14 to 0.27 pmol/well, was determined by using a monoclonal, anti-GPIIb-IIIa antibody (10E5). Maximum fibrinogen binding occurred after 60 minutes at 22 degrees C in the presence of 300 micrograms/ml fibrinogen, when 0.014 to 0.030 pmol fibrinogen bound per well. Assuming a 1:1 relationship between fibrinogen binding and GPIIb-IIIa occupancy, these data suggest that approximately 10% to 20% of immobilized GPIIb-IIIa was in an active confirmation. After 60 minutes, 65% +/- 13% of bound fibrinogen was resistant to dissociation by excess unlabeled fibrinogen, and 53% +/- 24% failed to dissociate with 10 mmol/L EDTA. Fibrinogen fragment D1 also bound irreversibly to immobilized GPIIb-IIIa (52% +/- 18%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed2000

Integrative analysis of protein interaction data.

We have developed a method for the integrative analysis of protein interaction data. It comprises clustering, visualization and data integration components. The method is generally applicable for all sequenced organisms. Here, we describe in detail the combination of protein interaction data in the yeast Saccharomyces cerevisiae with the functional classification of all yeast proteins. We evaluate the utility of the method by comparison with experimental data and deduce hypotheses about the functional role of so far uncharacterized proteins. Further applications of the integrative analysis method are discussed. The method presented here is powerful and flexible. We show that it is capable of mining large-scale data sets.

Animals↗
PubMed1986

An integrated model for the interaction of muscle relaxants with their antagonists.

An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions. Edrophonium arterial concentrations and twitch tension of the anterior tibialis muscle were measured. Both the integrated and the naive model were fit to the twitch tension data using a model with a hypothetical "effect" compartment. The integrated model consistently fit the twitch tension data better than the naive model; the sum of squared deviations was lower by 46, 45, 87, and 69%, respectively, with the integrated model than with the naive model. Also, in contrast to the naive model, the integrated model is capable of describing the interaction of the anticholinesterase agent and the neuromuscular blocking agent when the concentration of either varies with time.

Animals↗
PubMed2005

Comparative study on solvation free energy expressions in reference interaction site model integral equation theory.

The performance of the recently proposed partial wave (PW) free energy functional is compared with those of two previous expressions, Gaussian fluctuation (GF) and hypernetted chain (HNC), within the reference interaction site model framework. The applications to the calculations of ambient and supercritical water, solvation free energies of organic molecules, and partition coefficients clearly show that the PW and GF free energy expressions provide more reliable results than the HNC functional, indicating rather associative situations of geometry in ordinary liquids of medium-sized molecules.

Models, Theoretical↗
PubMed2006

pSTIING: a 'systems' approach towards integrating signalling pathways, interaction and transcriptional regulatory networks in inflammation and cancer.

pSTIING (http://pstiing.licr.org) is a new publicly accessible web-based application and knowledgebase featuring 65 228 distinct molecular associations (comprising protein-protein, protein-lipid, protein-small molecule interactions and transcriptional regulatory associations), ligand-receptor-cell type information and signal transduction modules. It has a particular major focus on regulatory networks relevant to chronic inflammation, cell migration and cancer. The web application and interface provide graphical representations of networks allowing users to combine and extend transcriptional regulatory and signalling modules, infer molecular interactions across species and explore networks via protein domains/motifs, gene ontology annotations and human diseases. pSTIING also supports the direct cross-correlation of experimental results with interaction information in the knowledgebase via the CLADIST tool associated with pSTIING, which currently analyses and clusters gene expression, proteomic and phenotypic datasets. This allows the contextual projection of co-expression patterns onto prior network information, facilitating the identification of functional modules in physiologically relevant systems.

Amino Acid Motifs↗
PubMed2006

Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53 interaction through an integrated, virtual database screening strategy.

An integrated, virtual database screening strategy has led to 7-[anilino(phenyl)methyl]-2-methyl-8-quinolinol (4, NSC 66811) as a novel inhibitor of the murine double minute 2 (MDM2)-p53 interaction. This quinolinol binds to MDM2 with a Ki of 120 nM and activates p53 in cancer cells with a mechanism of action consistent with targeting the MDM2-p53 interaction. It mimics three p53 residues critical in the binding to MDM2 and represents a promising new class of non-peptide inhibitors of the MDM2-p53 interaction.

Aniline Compounds↗
PubMed2000

COP I domains required for coatomer integrity, and novel interactions with ARF and ARF-GAP.

We performed a systematic mapping of interaction domains on COP I subunits to gain novel insights into the architecture of coatomer. Using the two-hybrid system, we characterize the domain structure of the alpha-, beta'-, epsilon-COP and beta-, gamma-, delta-, zeta-COP coatomer subcomplexes and identify links between them that contribute to coatomer integrity. Our results demonstrate that the domain organization of the beta-, gamma-, delta-, zeta-COP subcomplex and AP adaptor complexes is related. Through in vivo analysis of alpha-COP truncation mutants, we characterize distinct functional domains on alpha-COP. Its N-terminal WD40 domain is dispensable for yeast cell viability and overall coatomer function, but is required for KKXX-dependent trafficking. The last approximately 170 amino acids of alpha-COP are also non-essential for cell viability, but required for epsilon-COP incorporation into coatomer and maintainance of normal epsilon-COP levels. Further, we demonstrate novel direct interactions of coatomer subunits with regulatory proteins: beta'- and gamma-COP interact with the ARF-GTP-activating protein (GAP) Glo3p, but not Gcs1p, and beta- and epsilon-COP interact with ARF-GTP. Glo3p also interacts with intact coatomer in vitro.

ADP-Ribosylation Factors↗
PubMed1979

Integral membrane protein interaction with Triton cytoskeletons of erythrocytes.

The organization of erythrocyte membrane lipids and proteins has been studied following the release of cytoplasmic components with the non-ionic detergent Triton X-100. After detergent extraction, a detergent-resistant complex called the erythrocyte cytoskeleton is separated from detergent, solubilized lipid and protein by sucrose buoyant density sedimentation. In cytoskeletons prepared under isotonic conditions all of the major erythrocyte membrane proteins are retained except for the integral protein, glycophorin, which is quantitatively solubilized and another integral glycoprotein, band 3, which is only 60% removed. When cytoskeletons are prepared in hypertonic KCl solutions, band 3 is fully solubilized along with bands 2.1 and 4.2 and several minor components. The resulting cytoskeletons have the same morphology as those prepared in isotonic buffer but they are composed of only three major peripheral proteins, spectrin, actin and band 4.1. We have designated this peripheral protein complex the 'shell' of the erythrocyte membrane, and have shown that the attachment of band 3 to the shell satisfies the criteria for a specific interaction. Although Triton did affect erythrocyte shape, cytoskeleton lipid content and the activity of membrane proteases, there was no indication that Triton altered the attachment of band 3 to the shell. We suggest that band 3 attaches to the shell as part of a ternary complex of bands 2.1, 3 and 4.2.

Erythrocyte Membrane↗
PubMed2005

Saccharomyces cerevisiaeTSC11/AVO3 participates in regulating cell integrity and functionally interacts with components of the Tor2 complex.

Saccharomyces cerevisiae TSC11/AVO3 is an essential gene encoding one component of TORC2, a multi-protein complex of yeast Tor2p that also contains Lst8p, Avo1p, and Avo2p. Despite the proven physical association among TORC2 components, little is known about the functional linkage or cellular pathways these proteins act in. Here, we present genetic data linking the function of TSC11 to the regulation of cell integrity. Mutants carrying temperature-sensitive (ts) alleles in different regions of TSC11 displayed cell wall defects, evidenced by characteristic osmotic stabilizer-remediable cell lysis, susceptibility to trypan blue staining, and sensitivity to cell wall-digesting enzymes. Dosage suppression analysis identified different groups of genes in rescuing phenotypes of different tsc11(ts) mutants. AVO1 suppressed one class of mutants, whereas active PKC1, AVO2, and SLM1 partially rescued another. Our findings demonstrate functional connections among TORC2 components and we speculate that Tsc11p exerts its function via a Pkc1p-independent mechanism mediated through Avo1p, and a Pkc1p-dependent mechanism mediated through Avo2p and Slm1p.

Actins↗
PubMed1988

Interaction of amphiphiles with integral membrane proteins. II. A simple, minimal model for the nonspecific interaction of amphiphiles with the anion exchanger of the erythrocyte membrane.

In a previous paper we have reported on the structural perturbation of the erythrocyte membrane anion exchanger by a regular series of model amphiphiles, as shown by differential scanning calorimetry (Gruber, H.J. and Low, P.S., Biochim. Biophys. Acta, preceding article). Now the data are interpreted by a model in which the effects of amphiphile structure upon buffer-membrane partitioning are well separated from the dependence of the intrinsic potencies of membrane-bound amphiphiles upon amphiphile structure. The buffer-membrane partitioning situation was demonstrated to regularly change between extremes within a series of homologous amphiphiles, i.e. from a negligible to a predominant fraction of total amphiphile in the sample residing in the membrane. Based upon this demonstration a large number of reports on the chain length dependence of apparent potency could be reinterpreted in terms of chain length profiles of intrinsic potency, allowing for a comparison of the responses of various membrane proteins to homologous series of amphiphiles. The response patterns for chain length variation could be divided into three distinct classes: the intrinsic potency (i) can be independent of chain length over a very wide range of length, (ii) it can be rather independent up to a critical length where a sudden cut-off in potency occurs, or (iii) it can drop monotonically over a wide range of chain length. The intrinsic potency values of saturated fatty acids in destabilizing the anion exchanger were interpreted by very simple assumptions: only direct interactions between amphiphiles and target proteins and a simple amphiphile partition equilibrium between a pool of equivalent low affinity sites on the protein and the bulk lipid matrix. The observed monotonic decay of the intrinsic potency of saturated fatty acids with increasing chain length from C8 to C20 was translated into a constant increment of free energy by which each additional CH2 favors the transfer away from sites on the protein towards the bulk lipid matrix. Arguments were presented suggesting that the direct interaction between amphiphiles and target protein is completely nonspecific for alkyl chain length while the residual specificity for shorter over longer amphiphiles is due to the higher tendency of longer chains to preferentially bind in the bulk lipid matrix. Thus a completely new role of the lipid as a competitor, rather than a mediator, was postulated.

Cell Membrane↗
PubMed2006

The Saccharomyces cerevisiae spindle pole body (SPB) component Nbp1p is required for SPB membrane insertion and interacts with the integral membrane proteins Ndc1p and Mps2p.

The spindle pole body (SPB) in Saccharomyces cerevisiae functions to nucleate and organize spindle microtubules, and it is embedded in the nuclear envelope throughout the yeast life cycle. However, the mechanism of membrane insertion of the SPB has not been elucidated. Ndc1p is an integral membrane protein that localizes to SPBs, and it is required for insertion of the SPB into the nuclear envelope during SPB duplication. To better understand the function of Ndc1p, we performed a dosage suppressor screen using the ndc1-39 temperature-sensitive allele. We identified an essential SPB component, Nbp1p. NBP1 shows genetic interactions with several SPB genes in addition to NDC1, and two-hybrid analysis revealed that Nbp1p binds to Ndc1p. Furthermore, Nbp1p is in the Mps2p-Bbp1p complex in the SPB. Immunoelectron microscopy confirmed that Nbp1p localizes to the SPB, suggesting a function at this location. Consistent with this hypothesis, nbp1-td (a degron allele) cells fail in SPB duplication upon depletion of Nbp1p. Importantly, these cells exhibit a "dead" SPB phenotype, similar to cells mutant in MPS2, NDC1, or BBP1. These results demonstrate that Nbp1p is a SPB component that acts in SPB duplication at the point of SPB insertion into the nuclear envelope.

Alleles↗
PubMed1996

Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1.

At the nuclear envelope in higher eukaryotic cells, the nuclear lamina and the heterochromatin are adjacent to the inner nuclear membrane, and their attachment is presumably mediated by integral membrane proteins. In a yeast two-hybrid screen, the nucleoplasmic domain of lamin B receptor (LBR), an integral protein of the inner nuclear membrane, associated with two human polypeptides homologous to Drosophila HP1, a heterochromatin protein involved in position-effect variegation. LBR fusion proteins bound to HP1 proteins synthesized by in vitro translation and present in cell lysates. Antibodies against LBR also co-immunoprecipitated HP1 proteins from cell extracts. LBR can interact with chromodomain proteins that are highly conserved in eukaryotic species and may function in the attachment of heterochromatin to the inner nuclear membrane in cells.

Amino Acid Sequence↗
PubMed2001

Identification and characterization of a novel Golgi protein, GCP60, that interacts with the integral membrane protein giantin.

We demonstrated previously that the integral membrane protein giantin has the Golgi localization signal at the COOH-terminal cytoplasmic domain (Misumi, Y., Sohda, M., Tashiro, A., Sato, H., and Ikehara, Y. (2001) J. Biol. Chem. 276, 6867-6873). In the present study, using this domain as bait in the yeast two-hybrid screening system, we identified a novel protein interacting with giantin. The 3.6-kilobase mRNA encoding a 528-amino acid protein of 60 kDa designated GCP60 was ubiquitously expressed and was especially abundant in the testis and ovary. Immunofluorescence and immunoelectron microscopy confirmed that GCP60 was co-localized with giantin in the Golgi complex. GCP60 was found to be a peripheral protein associated with the Golgi membrane, where a COOH-terminal domain of GCP60 interacts with the COOH-terminal cytoplasmic domain of giantin. Overexpression of the COOH-terminal domain of GCP60 caused disassembly of the Golgi structure and blocked protein transport from the endoplasmic reticulum to the Golgi. Taken together, these results suggest that GCP60 is involved in the maintenance of the Golgi structure by interacting with giantin, affecting protein transport between the endoplasmic reticulum and the Golgi.

Adaptor Proteins, Signal Transducing↗