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At least 145 records · Page 8Linked to original sources
PubMed1996

Molecular interactions between transfected human TCR, immunodominant myelin basic protein peptide 152-165, and HLA-DR13.

Chimeric TCR transfectants expressing human extracellular sequences and murine intracellular/transmembrane sequences were generated to analyze the trimolecular interaction between myelin basic protein (MBP) autoantigen, HLA, and a TCR isolated from a patient with multiple sclerosis. Chimeric transfectants responded to TCR activation by CD3- and TCRBV22S1-specific mAbs and by superantigen. Additionally, chimeric transfectants responded to autoantigen-specific activation with MBP 152-165 when presented by DR(alpha,beta1*1301) independent of the CD4 adhesion molecule. Transfectants did not respond to Ag presented by other HLA-DR molecules, including the closely related DR(alpha,beta1*1302). In peptide-binding studies with a panel of serial alanine-substituted MBP peptides, HLA contact residues necessary for anchoring MBP 152-165 to DR(alpha,beta1*1301) were also defined: 154 (F), 159 (R), and 162 (R). The chimeric TCR transfectant's differential response to a similar panel of MBP analogues defined residues that interact with the TCR: 153 (I), 155 (K), 156 (L), 160 (D), and 161 (S). Analysis of molecular interactions, such as those described in this work, may be central to developing new strategies for suppressing Ag-specific responses in human autoimmune disease.

Amino Acid Sequence↗
PubMed2002

Molecular interactions of glycopeptide antibiotics investigated by affinity capillary electrophoresis and bioaffinity electrospray ionization-mass spectrometry.

Many analytical approaches are available to evaluate (bio)molecular interactions, all of which have their particular advantages and disadvantages. In recent years, two relatively new techniques have emerged that may be used by the bioanalytical community to evaluate such interactions, namely affinity capillary electrophoresis (ACE) and bioaffinity electrospray ionization-mass spectrometry (ESI-MS). In this paper, we describe and evaluate the use of both these techniques for the investigation of the interactions of glycopeptide antibiotics with peptides that mimic the bacterial cell wall binding site. We focus particularly on the effect of the sugar moieties attached to the antibiotic peptide backbone and on the noncovalent dimerization of these glycopeptide antibiotics.

Anti-Bacterial Agents↗
PubMed1998

Smooth muscle myosin mutants containing a single tryptophan reveal molecular interactions at the actin-binding interface.

Elucidation of the molecular details of the cyclic actomyosin interaction requires the ability to examine structural changes at specific sites in the actin-binding interface of myosin. To study these changes dynamically, we have expressed two mutants of a truncated fragment of chicken gizzard smooth muscle myosin, which includes the motor domain and essential light chain (MDE). These mutants were engineered to contain a single tryptophan at (Trp-546) or near (Trp-625) the putative actin-binding interface. Both 546- and 625-MDE exhibited actin-activated ATPase and actin-binding activities similar to wild-type MDE. Fluorescence emission spectra and acrylamide quenching of 546- and 625-MDE suggest that Trp-546 is nearly fully exposed to solvent and Trp-625 is less than 50% exposed in the presence and absence of ATP, in good agreement with the available crystal structure data. The spectrum of 625-MDE bound to actin was quite similar to the unbound spectrum indicating that, although Trp-625 is located near the 50/20-kDa loop and the 50-kDa cleft of myosin, its conformation does not change upon actin binding. However, a 10-nm blue shift in the peak emission wavelength of 546-MDE observed in the presence of actin indicates that Trp-546, located in the A-site of the lower 50-kDa subdomain of myosin, exists in a more buried environment and may directly interact with actin in the rigor acto-S1 complex. This change in the spectrum of Trp-546 constitutes direct evidence for a specific molecular interaction between residues in the A-site of myosin and actin.

Actins↗
PubMed1999

The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein.

1 The kinetics and nature of equilibrium binding were used to characterize the molecular interaction of the anthranilic acid derivative [3H]-XR9576 with the multidrug resistance P-glycoprotein (P-gp). XR9576 displayed specific high-affinity binding to P-gp (Bmax = 275 pmol mg-1, Kd = 5.1 nM). The transport substrates [3H]-vinblastine and [3H]-paclitaxel displayed 4 fold and 20 fold lower affinity respectively for P-gp. The duration of action of XR9576 with P-gp was increased in comparison to that of vinblastine which displayed a slower rate of association and a faster dissociation rate. 2 The relative affinities of several modulators and transport substrates to interact with P-gp were determined from displacement drug equilibrium binding assays. Vinblastine and paclitaxel could only fractionally displace [3H]-XR9576 binding, displaying Ki values significantly different from their measured Kd values. This suggests a non-competitive interaction between XR9576 and the P-gp substrates vinblastine and paclitaxel. 3 XR9576 was shown to be a potent modulator of P-gp mediated [3H]-vinblastine and [3H]-paclitaxel transport as it increased the steady-state accumulation of these cytotoxics in CHrB30 cells to levels observed in non-P-gp-expressing AuxB1 cells (EC50 = 487+/-50 nM). This inhibition of drug transport is not mediated through competition for transport since [3H]-XR9576 accumulation was not influenced by P-gp expression or function. 4 These results demonstrate that the P-gp modulator XR9576 exhibits greater selectivity, duration of inhibition and potency of interaction with this transporter than any other reported modulators. Several lines of evidence suggest that XR9576 inhibits P-gp function by binding at a site which is distinct from the site of interaction of transport substrates. The two sites may be classified as serving modulatory or transport functions.

ATP Binding Cassette Transporter, Subfamily B↗
PubMedDate not supplied

Molecular interactions between nucleic acids and antitumor substances by Raman and NMR spectroscopy.

1-Methyladenosine (1-MeAdo) and protonated 1-Methyladenosine (1-MeAdo.H+) were chosen as a model to study the molecular interactions between the carcinogen dimethylsulphate (DMS) and the base adenine, and the interactions between the antitumoral electrophilic cis-diamminedichlorophatinum (II) (cis-Pt) and the methylation product of the base, respectively. Raman and multinuclear NMR studies show the molecular perturbations caused by the carcinogen on the base and those of the antitumoral substance on the reaction product base-carcinogen.

Adenosine↗
PubMed2000

Molecular interactions of peptides with phospholipid vesicle membranes as studied by fluorescence correlation spectroscopy.

Interactions of the peptides melittin and magainin with phospholipid vesicle membranes have been studied using fluorescence correlation spectroscopy. Molecular interactions of melittin and magainin with phospholipid membranes are performed in rhodamine-entrapped vesicles (REV) and in rhodamine-labelled phospholipid vesicles (RLV), which did not entrap free rhodamine inside. The results demonstrate that melittin makes channels into vesicle membranes since exposure of melittin to vesicles causes rhodamine release only from REV but not from RLV. It is obvious that rhodamine can not be released from RLV because the inside of RLV is free of dye molecules. In contrast, magainin breaks vesicles since addition of magainin to vesicles results in rhodamine release from both REV and RLV. As the inside of RLV is free of rhodamine, the appearance of rhodamine in solution confirms that these vesicles are broken into rhodamine-labelled phospholipid fragments after addition of magainin. This study is of pharmaceutical significance since it will provide insights that fluorescence correlation spectroscopy can be used as a rapid protocol to test incorporation and release of drugs by vesicles.

Liposomes↗
PubMed2006

Approaching the proteoglycome: molecular interactions of proteoglycans and their functional output.

[Image: see text] Through their diverse core protein modules and glycan/glycosaminoglycan moieties, proteoglycans may engage in numerous cellular and molecular interactions which are dispensable during embryogenesis, are essential for the maintenance of a healthy state and are prone to modulation in pathological conditions. Proteoglycan interactions may involve binding to other structural components of the ECM, to cell surface receptors, to membrane-associated components, and to soluble signaling molecules, which through this interaction may become entrapped in the ECM or sequestered at the cell surface. Understanding of these multiple interplays is therefore of paramount importance and requires a detailed mapping through what we define as the proteoglycome.

Extracellular Matrix↗
PubMed2004

Molecular interactions regulate BCR signal inhibition by CD22 and CD72.

The inhibitory coreceptors CD22 and CD72 downmodulate B-cell receptor (BCR) signaling and function as a molecular switch, determining whether antigen-stimulated B cells undergo apoptosis or proliferation. These coreceptors carry an intrinsic property for associating with the BCR, and this association is crucial for the initiation of signal inhibition through phosphorylation of these coreceptors by BCR-associated kinases. Recent findings have demonstrated that signal inhibition by these coreceptors is regulated by ligands for the coreceptors and by molecules binding to the coreceptors or the BCR. Moreover, signal inhibition by CD22 depends on the BCR isotype. These findings suggest a dynamic regulation of these coreceptors through molecular interactions on the B-cell surface.

Animals↗
PubMed2006

Study of weak molecular interactions through thermodynamic mixing properties.

The electron donor-acceptor abilities of some cyclic ethers (tetrahydropyran or tetrahydrofuran), benzene, and halobenzenes (fluorobenzene or chlorobenzene) and the molecular interactions between these compounds have been investigated through a wide set of thermodynamic mixing properties of their mixtures. The mixing properties have been derived from experimental measurements of density, speed of sound, refractive index, surface tension, heat of mixing, and vapor-liquid equilibrium at the temperature of 298.15 K.

Journal Article↗
PubMed2004

Molecular interaction of retinoic acid receptors with coregulators PCAF and RIP140.

p300/CBP-associating factor (PCAF) is a ligand-dependent coactivator, whereas receptor-interacting protein 140 (RIP140) is a ligand-dependent negative coregulator for retinoic acid (RA) receptor (RAR) and retinoid X receptor (RXR). To compare these molecular interactions and to determine the effect of RXR ligands, we focus on PCAF/RAR/RXR complex formation in this study for a comparison to RIP140/RAR/RXR complex formation. The LBD of RXR is identified as its primary PCAF-interacting motif. BIAcore studies determine the Kd of RAR/RXR association with PCAF as 9.35 nM in the presence of RXR ligand AGN194204, and 47.2 nM in the absence of ligand. Cross-linking study demonstrates tri-molecular complex consisting of one RAR/RXR pair and one PCAF. In competition experiments, RIP140 strongly competes with PCAF for interaction with RAR/RXR both in vitro and in vivo. Chromatin immunoprecipitation demonstrates recruitment of RIP140 and PCAF to the endogenous RA-regulated gene, the RARbeta2 promoter. This study presents kinetic evidence for competition of RIP140 with PCAF for ligand-dependent interactions with RAR/RXR, and provides kinetic explanation for the suppressive activity of RIP140 in RA-activated gene expression.

Acetyltransferases↗
PubMed2003

Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity.

Receptor interacting protein 140 (RIP140) interacts with retinoic acid receptor (RAR) and retinoid X receptor (RXR) constitutively, but hormone binding enhances this interaction. The ligand-independent interaction is mediated by the amino and central regions of RIP140 which contain a total of nine copies of the LXXLL motif, whereas the agonist-induced interaction is mediated by its carboxyl terminus which contains a novel motif (1063-1076, LTKTNPILYYMLQK). The ligand-independent interaction could be enhanced slightly by agonists, whereas the ligand-dependent interaction was strictly agonist dependent for both RAR and RXR. In the context of heterodimers, ligand occupancy of RXR played a more dominant role for both molecular interaction and biological activity of RIP140. Competition and mutation studies demonstrated an essential role for (1067)Asn and (1073)Met for a ligand-dependent interaction. A model was proposed to address the constitutive and agonist-dependent interaction of RIP140 with RAR/RXR.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Molecular interactions between human cytochrome P450 1A2 and flavone derivatives.

Activation by human cytochrome P450 1A2 (hCYP1A2) of heterocyclic amines is assumed to trigger of a number of carcinogenic processes. In this work, a group of natural inhibitors of human cytochrome P450 1A2 reported in literature has been theoretically analysed. These consist of flavone hydroxylated derivatives, natural compounds that exist in plants and associated products. Different theoretical/computational tools were used to describe the specific molecular interactions between these compounds and hCYP1A2. Based on this analysis, a method is proposed for helping the selection of specific molecular features that enhance protein-inhibitor interaction.

Binding Sites↗
PubMed2006

Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together.

Protein interaction data exists in a number of repositories. Each repository has its own data format, molecule identifier and supplementary information. Michigan Molecular Interactions (MiMI) assists scientists searching through this overwhelming amount of protein interaction data. MiMI gathers data from well-known protein interaction databases and deep-merges the information. Utilizing an identity function, molecules that may have different identifiers but represent the same real-world object are merged. Thus, MiMI allows the users to retrieve information from many different databases at once, highlighting complementary and contradictory information. To help scientists judge the usefulness of a piece of data, MiMI tracks the provenance of all data. Finally, a simple yet powerful user interface aids users in their queries, and frees them from the onerous task of knowing the data format or learning a query language. MiMI allows scientists to query all data, whether corroborative or contradictory, and specify which sources to utilize. MiMI is part of the National Center for Integrative Biomedical Informatics (NCIBI) and is publicly available at: http://mimi.ncibi.org.

Databases, Protein↗
PubMed2004

Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks.

Intrinsic (innate) and acquired (adaptive) resistance to chemotherapy critically limits the outcome of cancer treatments. For many years, it was assumed that the interaction of a drug with its molecular target would yield a lethal lesion, and that determinants of intrinsic drug resistance should therefore be sought either at the target level (quantitative changes or/and mutations) or upstream of this interaction, in drug metabolism or drug transport mechanisms. It is now apparent that independent of the factors above, cellular responses to a molecular lesion can determine the outcome of therapy. This review will focus on programmed cell death (apoptosis) and on survival pathways (Bcl-2, Apaf-1, AKT, NF-kappaB) involved in multidrug resistance. We will present our molecular interaction mapping conventions to summarize the AKT and IkappaB/NF-kappaB networks. They complement the p53, Chk2 and c-Abl maps published recently. We will also introduce the 'permissive apoptosis-resistance' model for the selection of multidrug-resistant cells.

Animals↗
PubMed2005

Molecular interactions between dendritic cells and Salmonella: escape from adaptive immunity and implications on pathogenesis.

Dendritic cells (DCs) constitute the link between innate and adaptive immunity by directly recognizing pathogen-associated molecular patterns (PAMPs) on bacteria and by processing and presenting bacterial antigens to T cells. Recognition of PAMPs renders DCs as professional antigen-presenting cells with the ability to prime naive T cells and to initiate the adaptive immune response against pathogen-derived antigens. For this reason, any interference with DC function might be advantageous for bacterial survival and dissemination. Identification of the molecular interactions occurring between DCs and bacterial pathogens is necessary to understand the mechanisms that virulent bacteria have evolved to prevent recognition by the adaptive immune system. This could be helpful in the identification of possible new targets that might lead to the design of effective therapies aimed at preventing or treating serious infections by these pathogens. In this article, we focus on Salmonella enterica serovar Typhimurium, the causative agent of typhoid-like disease in the mouse, and how it is able to escape from DC-mediated antigen presentation by avoiding lysosomal degradation. This feature of virulent Salmonella requires the functional expression of the Type Three Secretion System (TTSS) and effector proteins encoded within the Salmonella pathogenicity island 2 (SPI-2). Recent studies have demonstrated that impairment of DC function by the activity of SPI-2 gene products is crucial for Salmonella pathogenesis.

Animals↗
PubMed2004

Insight into molecular interactions between two PB1 domains.

Specific protein-protein interactions play crucial roles in the regulation of any biological process. Recently, a new protein-protein interaction domain termed PB1 (Phox and Bem1) was identified, which is conserved throughout evolution and present in diverse proteins functioning in signal transduction, cell polarity and survival. Here, we investigated the structure and molecular interactions of the PB1 heterodimer complex composed of the PB1 domains of the yeast proteins Bem1 and Cdc24. A structural model of the Cdc24 PB1 was built by homology modeling and molecular dynamics simulations, and experimentally validated by 15N nuclear Overhauser effect spectroscopy (NOESY)-heteronuclear single quantum coherence (HSQC) analysis. Residues at the interface of the complex for both proteins were identified by NMR titration experiments. A model of the heterodimer was obtained by docking of the two PB1 domains with HADDOCK, which applies ambiguous interaction restraints on residues at the interface to drive the docking procedure. The refined model was validated by site-directed mutagenesis on both Bem1 and Cdc24. Finally, the docking was repeated from the newly published NMR structure of Cdc24, allowing us to assess the performance of homology-based docking. Our results provide insight into the molecular structure of the Bem1-Cdc24 PB1-mediated heterodimer, which allowed identification of critical residues at the binding interface.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Analysis of the molecular interaction of glycosylated proteins with rabbit liver asialoglycoprotein receptors using surface plasmon resonance spectroscopy.

A sensitive, accurate, and efficient biosensor analysis using surface plasmon resonance (SPR) spectroscopy was used for delineating the molecular interaction between rabbit liver asialoglycoprotein receptors (ASGPR) and glycosylated proteins. Isolated rabbit liver ASGPR obtained by affinity column chromatography was dissolved in buffer solution containing TritonX-100 and immobilized on the SPR sensor chip by amine coupling. The SPR study demonstrated that the association rate constants (ka) of galactosylated proteins with ASGPR are dependent on the number of galactose residues, while the dissociation rate constants (kd) are influenced not only by the surface density of the galactose moieties but also by their steric configuration. In addition, it was demonstrated that D-fucosylated BSA had a higher binding affinity to ASGPR than Gal-BSA, when the degree of sugar modification was equivalent.

Animals↗
PubMed2003

Fluorescence resonance energy transfer analysis of cytochromes P450 2C2 and 2E1 molecular interactions in living cells.

The molecular organization of microsomal cytochromes P450 (P450s) and formation of complexes with P450 reductase have been studied previously with isolated proteins and in reconstituted systems. Although these studies demonstrated that some P450s oligomerize in vitro, neither oligomerization nor interactions of P450 with P450 reductase have been studied in living cells. Here we have used fluorescence resonance energy transfer (FRET) to study P450 oligomerization and binding to P450 reductase in live transfected cells. Cytochrome P450 2C2, but not P450 2E1, forms homo-oligomeric structures, and this self-association is mediated by the signal-anchor sequence. Because P450 2C2, in contrast to P450 2E1, is directly retained in the endoplasmic reticulum (ER), these results could suggest that oligomerization may prevent transport from the ER. However, P450 2C1 signal-anchor sequence chimera defective in ER retention also formed oligomers, and chimera containing the cytoplasmic domain of P450 2C2, which is directly retained in the ER, did not exhibit self-oligomerization, which indicates that oligomerization is not correlated with direct retention. By using FRET, we have also detected binding of P450 2C2 and P450 2E1 to P450 reductase. In contrast to self-oligomerization, the catalytic domain can mediate an interaction of P450 2C2 with P450 reductase. These results suggest that microsomal P450s may differ in their quaternary structure but that these differences do not detectably affect interaction with the reductase or transport from the ER.

Animals↗