Search results for "binding"
showing 10 items of 3896 documents
Autoregulation of NFATc1/A Expression Facilitates Effector T Cells to Escape from Rapid Apoptosis
2002
AbstractThreshold levels of individual NFAT factors appear to be critical for apoptosis induction in effector T cells. In these cells, the short isoform A of NFATc1 is induced to high levels due to the autoregulation of the NFATc1 promoter P1 by NFATs. P1 is located within a CpG island in front of exon 1, represents a DNase I hypersensitive chromatin site, and harbors several sites for binding of inducible transcription factors, including a tandemly arranged NFAT site. A second promoter, P2, before exon 2, is not controlled by NFATs and directs synthesis of the longer NFATc1/B+C isoforms. Contrary to other NFATs, NFATc1/A is unable to promote apoptosis, suggesting that NFATc1/A enhances eff…
Expression of the Acetylcholine Receptor α-Subunit Gene is Associated with Paraneoplastic Myasthenia Gravis in Mixed Thymoma
2000
Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction [1]. The muscular AChR has been extensively characterized [2], but the etiology of MG is still obscure. Whether the muscular AChR or another (auto)antigen plays a role during the initiation of MG is unknown [3]. The muscular AChR is a pentameric ion channel composed of four different subunits. The α-subunit contains the acetylcholine binding site and the main epitopes recognized by MG autoantibodies [2]. The human muscle AChR α-subunit exists as two isoforms, P3A- and P3A+ [4]. This is a result of alternative splicing of the P3A exon located betwee…
Midgut aminopeptidase N isoforms from Ostrinia nubilalis: Activity characterization and differential binding to Cry1Ab and Cry1Fa proteins from Bacil…
2013
Aminopeptidase N (APN) isoforms from Lepidoptera are known for their involvement in the mode of action of insecticidal Cry proteins from Bacillus thuringiensis. These enzymes belong to a protein family with at least eight different members that are expressed simultaneously in the midgut of lepidopteran larvae. Here, we focus on the characterization of the APNs from Ostrinia nubilalis (OnAPNs) to identify potential Cry receptors. We expressed OnAPNs in insect cells using a baculovirus system and analyzed their enzymatic activity by probing substrate specificity and inhibitor susceptibility. The interaction with Cry1Ab and Cry1Fa proteins (both found in transgenic insect-resistant maize) was …
Centrins in retinal photoreceptor cells: regulators in the connecting cilium.
2008
Changes in the intracellular Ca2+ concentration regulate the visual signal transduction cascade directly or more often indirectly through Ca2+-binding proteins. Here we focus on centrins, which are members of a highly conserved subgroup of the EF-hand superfamily of Ca2+-binding proteins in photoreceptor cells of the vertebrate retina. Centrins are commonly associated with centrosome-related structures. In mammalian retinal photoreceptor cells, four centrin isoforms are expressed as prominent components in the connecting cilium linking the light-sensitive outer segment compartment with the metabolically active inner segment compartment. Our data indicate that Ca2+-activated centrin isoforms…
Negative cooperativity in Root-effect hemoglobins: role of heterogeneity.
2011
In some animals, the oxygen transport capacity of blood decreases when pH is lowered, yielding oxygen binding curves with Hill-coefficients smaller than unity. This so-called Root effect is observed in several fishes and is important for creating large oxygen partial pressures locally, for example in the swim bladder. While there is general agreement on the physiological advantages of this effect, its molecular basis remains ambiguous. Various studies show that isoforms of hemoglobins usually are present in the hemolymph, when the Root effect is observed. Here, we show that in such a case the mixture of these isoforms can exhibit apparent negative cooperativity, although each component take…
Claudin-18 gene structure, regulation, and expression is evolutionary conserved in mammals
2011
Claudin-18 isoform 2 (CLDN18.2) is one of the few members of the human claudin family of tight junction molecules with strict restriction to one cell lineage. The objective of the current study was to compare molecular structure and tissue distribution of this gastrocyte specific molecule in mammals. We show here that the CLDN18.2 protein sequence is highly conserved, in particular with regard to functionally relevant domains in mouse, rat, rabbit, dog, monkey and human and also in lizards. Moreover, promoter regions of orthologs are highly homologous, including the binding site of the transcription factor cyclic AMP-responsive element binding protein (CREB), which is known to regulate acti…
Hsp70 is required for optimal cell proliferation in mouse A6 mesoangioblast stem cells.
2009
Mouse Hsp70 (70 kDa heat shock protein) is preferentially induced by heat or stress stimuli. We previously found that Hsp70 is constitutively expressed in A6 mouse mesoangioblast stem cells, but its possible role in these cells and the control of its basal transcription remained unexplored. Here we report that in the absence of stress, Ku factor is able to bind the HSE (heat shock element) consensus sequence in vitro, and in vivo it is bound to the proximal hsp70 promoter. In addition, we show that constitutive hsp70 transcription depends on the co-operative interaction of different factors such as Sp1 (specificity protein 1) and GAGA-binding protein with Ku factor, which binds the HSE cons…
Experimental-Like Affinity Constants and Enantioselectivity Estimates from Flexible Docking
2012
Experimental-like affinity constants and enantioselectivity estimates, not predicted so far computationally, were obtained using a novel flexible modeling/docking combined strategy. The S- and R-warfarin-human serum albumin (HSA, site I) complexes were used as an interaction model. The process for a verified estimation includes the following: (i) ionized open chain forming at physiological pH (a recent focus); (ii) conformational search (molecular mechanics and Monte Carlo methods); (iii) rigid protein-flexible ligand docking (GlideXP) generating low energy paired S- and R-poses; (iv) graphical comparison against the X-ray crystal structure (unsatisfactory verification step); (v) quantum po…
ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated…
2022
Abstract Background Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated by microglia contributes to ALS pathogenesis. This microglial activation is evident in post-mortem brain tissues and neuroimaging data from patients with ALS. However, the role of microglia in the pathogenesis and progression of amyotrophic lateral sclerosis remains unclear, partly due to the lack of a model system that is able to faithfully recapitulate the clinical pathology of ALS. To address this shortcoming, we describe an approach that generates monocyte-derived mi…
Calcium binding and ionic conduction in single conical nanopores with polyacid chains: model and experiments.
2012
Calcium binding to fixed charge groups confined over nanoscale regions is relevant to ion equilibrium and transport in the ionic channels of the cell membranes and artificial nanopores. We present an experimental and theoretical description of the dissociation equilibrium and transport in a single conical nanopore functionalized with pH-sensitive carboxylic acid groups and phosphonic acid chains. Different phenomena are simultaneously present in this basic problem of physical and biophysical chemistry: (i) the divalent nature of the phosphonic acid groups fixed to the pore walls and the influence of the pH and calcium on the reversible dissociation equilibrium of these groups; (ii) the asym…