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Multiple Interactions (multiple + interaction)
Selected AbstractsThe HAL3-PPZ1 dependent regulation of nonsense suppression efficiency in yeast and its influence on manifestation of the yeast prion-like determinant [ISP+]GENES TO CELLS, Issue 4 2007Anna Aksenova The efficiency of stop codons read-through in yeast is controlled by multiple interactions of genetic and epigenetic factors. In this study, we demonstrate the participation of the Hal3-Ppz1 protein complex in regulation of read-through efficiency and manifestation of non-Mendelian anti-suppressor determinant [ISP+]. Over-expression of HAL3 in [ISP+] strain causes nonsense suppression, whereas its inactivation displays as anti-suppression of sup35 mutation in [isp,] strain. [ISP+] strains carrying hal3, deletion cannot be cured from [ISP+] in the presence of GuHCl. Since Hal3p is a negative regulatory subunit of Ppz1 protein phosphatase, consequences of PPZ1 over-expression and deletion are opposite to those of HAL3. The observed effects are mediated by the catalytic function of Ppz1 and are probably related to the participation of Ppz1 in regulation of eEF1B, elongation factor activity. Importantly, [ISP+] status of yeast strains is determined by fluctuation in Hal3p level, since [ISP+] strains have less Hal3p than their [isp,] derivatives obtained by GuHCl treatment. A model considering epigenetic (possibly prion) regulation of Hal3p amount as a mechanism underlying [ISP+] status of yeast cell is suggested. [source] Use of Genetic Analyses to Refine Phenotypes Related to Alcohol Tolerance and DependenceALCOHOLISM, Issue 2 2001John C. Crabbe Various explanations for the dependence on alcohol are attributed to the development of tolerance to some of alcohol's effects, alterations in sensitivity to its rewarding effects, and unknown pathologic consequences of repeated exposure. All these aspects of dependence have been modeled in laboratory rodents, and these studies have consistently shown a significant influence of genetics. Genetic mapping studies have identified the genomic location of the specific genes for some of these contributing phenotypes. In addition, studies have shown that some genes in mice seem to affect both alcohol self-administration and alcohol withdrawal severity: genetic predisposition to high levels of drinking covaries with genetic predisposition to low withdrawal severity, and vice versa. Finally, the role of genetic background on which genes are expressed is important, as are the specifics of the environment in which genetically defined animals are tested. Understanding dependence will require disentangling the multiple interactions of many contributing phenotypes, and genetic analyses are proving very helpful. However, rigorous understanding of both gene-gene and gene-environment interactions will be required to interpret genetic experiments clearly. [source] Translation repression by an RNA polymerase elongation complexMOLECULAR MICROBIOLOGY, Issue 3 2004Helen R. Wilson Summary Bacteriophage , N and bacterial Nus proteins together with a unique site NUT in the leader of the early viral N gene transcript bind RNA polymerase (RNAP) and form a highly processive antitermination complex; N bound at NUT also represses N translation. In this study, we investigate whether N and NUT cause N translation repression as part of the antitermination complex by testing conditions that inhibit the formation of the N-modified transcription complex for their effect on N-mediated translation repression. We show that nus and nut mutations that in combination destabilize multiple interactions in the antitermination complex prevent N-mediated translation repression. Likewise, transcription of the nut-N region by T7 RNAP, which does not lead to the assembly of an effective antitermination complex when N is supplied, eliminates translation repression. We also demonstrate that a unique mutant , subunit of RNAP reduces N-mediated translation repression, and that overexpression of transcription factor NusA suppresses this defect. We conclude that the N-modified RNAP transcription complex is necessary to repress N translation. [source] Identification of transient hub proteins and the possible structural basis for their multiple interactionsPROTEIN SCIENCE, Issue 1 2008Miho Higurashi Abstract Proteins that can interact with multiple partners play central roles in the network of protein,protein interactions. They are called hub proteins, and recently it was suggested that an abundance of intrinsically disordered regions on their surfaces facilitates their binding to multiple partners. However, in those studies, the hub proteins were identified as proteins with multiple partners, regardless of whether the interactions were transient or permanent. As a result, a certain number of hub proteins are subunits of stable multi-subunit proteins, such as supramolecules. It is well known that stable complexes and transient complexes have different structural features, and thus the statistics based on the current definition of hub proteins will hide the true nature of hub proteins. Therefore, in this paper, we first describe a new approach to identify proteins with multiple partners dynamically, using the Protein Data Bank, and then we performed statistical analyses of the structural features of these proteins. We refer to the proteins as transient hub proteins or sociable proteins, to clarify the difference with hub proteins. As a result, we found that the main difference between sociable and nonsociable proteins is not the abundance of disordered regions, in contrast to the previous studies, but rather the structural flexibility of the entire protein. We also found greater predominance of charged and polar residues in sociable proteins than previously reported. [source] ,Bubble chamber model' of fast atom bombardment induced processesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2003Marina V. Kosevich A hypothesis concerning FAB mechanisms, referred to as a ,bubble chamber FAB model', is proposed. This model can provide an answer to the long-standing question as to how fragile biomolecules and weakly bound clusters can survive under high-energy particle impact on liquids. The basis of this model is a simple estimation of saturated vapour pressure over the surface of liquids, which shows that all liquids ever tested by fast atom bombardment (FAB) and liquid secondary ion mass spectrometry (SIMS) were in the superheated state under the experimental conditions applied. The result of the interaction of the energetic particles with superheated liquids is known to be qualitatively different from that with equilibrium liquids. It consists of initiation of local boiling, i.e., in formation of vapour bubbles along the track of the energetic particle. This phenomenon has been extensively studied in the framework of nuclear physics and provides the basis for construction of the well-known bubble chamber detectors. The possibility of occurrence of similar processes under FAB of superheated liquids substantiates a conceptual model of emission of secondary ions suggested by Vestal in 1983, which assumes formation of bubbles beneath the liquid surface, followed by their bursting accompanied by release of microdroplets and clusters as a necessary intermediate step for the creation of molecular ions. The main distinctive feature of the bubble chamber FAB model, proposed here, is that the bubbles are formed not in the space and time-restricted impact-excited zone, but in the nearby liquid as a ,normal' boiling event, which implies that the temperature both within the bubble and in the droplets emerging on its burst is practically the same as that of the bulk liquid sample. This concept can resolve the paradox of survival of intact biomolecules under FAB, since the part of the sample participating in the liquid,gas transition via the bubble mechanism has an ambient temperature which is not destructive for biomolecules. Another important feature of the model is that the timescale of bubble growth is no longer limited by the relaxation time of the excited zone (,10,12,s), but rather resembles the timescale characteristic of common boiling, sufficient for multiple interactions of gas molecules and formation of clusters. Further, when the bubbles burst, microdroplets are released, which implies that FAB processes are similar to those in spraying techniques. Thus, two processes contribute to the ion production, namely, release of volatile solvent clusters from bubbles and of non-volatile solute from sputtered droplets. This view reconciles contradictory views on the dominance of either gas-phase or liquid-phase effects in FAB. Some other effects, such as suppression of all other ions by surface-active compounds, are consistent with the suggested model. Copyright © 2003 John Wiley & Sons, Ltd. [source] Interactions between multiple sources of short-term plasticity during evoked and spontaneous activity at the rat calyx of HeldTHE JOURNAL OF PHYSIOLOGY, Issue 13 2008Matthias H. Hennig Sustained activity at most central synapses is accompanied by a number of short-term changes in synaptic strength which act over a range of time scales. Here we examine experimental data and develop a model of synaptic depression at the calyx of Held synaptic terminal that combines many of these mechanisms (acting at differing sites and across a range of time scales). This new model incorporates vesicle recycling, facilitation, activity-dependent vesicle retrieval and multiple mechanisms affecting calcium channel activity and release probability. It can accurately reproduce the time course of experimentally measured short-term depression across different stimulus frequencies and exhibits a slow decay in EPSC amplitude during sustained stimulation. We show that the slow decay is a consequence of vesicle release inhibition by multiple mechanisms and is accompanied by a partial recovery of the releasable vesicle pool. This prediction is supported by patch-clamp data, using long duration repetitive EPSC stimulation at up to 400 Hz. The model also explains the recovery from depression in terms of interaction between these multiple processes, which together generate a stimulus-history-dependent recovery after repetitive stimulation. Given the high rates of spontaneous activity in the auditory pathway, the model also demonstrates how these multiple interactions cause chronic synaptic depression under in vivo conditions. While the magnitude of the depression converges to the same steady state for a given frequency, the time courses of onset and recovery are faster in the presence of spontaneous activity. We conclude that interactions between multiple sources of short-term plasticity can account for the complex kinetics during high frequency stimulation and cause stimulus-history-dependent recovery at this relay synapse. [source] A Multimeric Quinacrine Conjugate as a Potential Inhibitor of Alzheimer's ,-Amyloid Fibril FormationCHEMBIOCHEM, Issue 6 2008Gunnar T. Dolphin Abstract Amyloid formation and accumulation of the amyloid ,-peptide (A,) in the brain is associated with Alzheimer's disease (AD) pathogenesis. Therefore, among the therapeutic approaches in development to fight the disease, the direct inhibition of the A, self-assembly process is currently widely investigated and is one of the most promising approaches. In this study we investigated the potential of a multimeric display of quinacrine derivatives, as compared to the monomer quinacrine, as a design principal for a novel class of inhibitors against A, fibril formation. The presented multimeric conjugate exhibits a cluster of four quinacrine derivatives on a rigid cyclopeptidic scaffold. Herein is reported the synthesis of the conjugate, together with the in vitro inhibitory evaluation of A,1,40 fibrils using the thioflavin T fluorescence assay, and imaging with atomic force microscopy. Our data show that the multimeric compound inhibits A,1,40 fibril formation with an IC50 value of 20±10 ,M, which contrasts with the nonactive monomeric analogue. This work suggests that assembling multiple copies of acridine moieties to a central scaffold, for multiple interactions, is a promising strategy for the engineering of inhibitors against A, fibril formation. [source] | |||||||||||||