Search results for "DOMAIN"

Widespread selection for high and low secondary structure in coding sequences across all domains of life

2019

AbstractCodon composition, GC-content and local RNA secondary structures can have a profound effect on gene expression and mutations affecting these parameters, even though they do not alter the protein sequence, are not neutral in terms of selection. Although evidence exists that in some cases selection favors more stable RNA secondary structures, we currently lack a concrete idea of how many genes are affected within a species, and if this is a universal phenomenon in nature.We searched for signs of structural selection in a global manner, analyzing a set of one million coding sequences from 73 species representing all domains of life, as well as viruses, by means of our newly developed s…

2013

The cytoplasmic PASC domain of the fumarate responsive sensor kinase DcuS of Escherichia coli links the transmembrane to the kinase domain. PASC is also required for interaction with the transporter DctA serving as a cosensor of DcuS. Earlier studies suggested that PASC functions as a hinge and transmits the signal to the kinase. Reorganizing the PASC dimer interaction and, independently, removal of DctA, converts DcuS to the constitutive ON state (active without fumarate stimulation). ON mutants were categorized with respect to these two biophysical interactions and the functional state of DcuS: type I-ON mutations grossly reorganize the homodimer, and decrease interaction with DctA. Type …

Effects of sulindac sulfide on the membrane architecture and the activity of gamma-secretase.

2007

gamma-Secretase is a membrane-embedded multi-protein complex that catalyzes the final cut of the Alzheimer's disease-related amyloid precursor protein (APP) to amyloid-beta peptides of variable length (37-43 amino acids) via an unusual intramembrane cleavage. Recent findings propose that some commonly used non-steroidal anti-inflammatory drugs (NSAIDs) have the ability to modulate specifically gamma-secretase activity without inhibiting the enzyme as a whole. These drugs may shift the processing of APP from the longer amyloid-beta 42 peptide towards shorter, less fibrillogenic and less toxic amyloid-beta species. We hypothesize that gamma-secretase activity, as an enzyme that is strictly as…

2013

Protein kinases constitute an attractive family of enzyme targets with high relevance to cell and disease biology. Small molecule inhibitors are powerful tools to dissect and elucidate the function of kinases in chemical biology research and to serve as potential starting points for drug discovery. However, the discovery and development of novel inhibitors remains challenging. Here, we describe a structure-based de novo design approach that generates novel, hinge-binding fragments that are synthetically feasible and can be elaborated to small molecule libraries. Starting from commercially available compounds, core fragments were extracted, filtered for pharmacophoric properties compatible w…

Perturbed interactions of mutant proteolipid protein/DM20 with cholesterol and lipid rafts in oligodendroglia: implications for dysmyelination in spa…

2006

Missense mutations in the humanPLP1gene lead to dysmyelinating diseases with a broad range of clinical severity, ranging from severe Pelizaeus–Merzbacher disease (PMD) to milder spastic paraplegia type 2 (SPG-2). The molecular pathology has been generally attributed to endoplasmic reticulum (ER) retention of misfolded proteolipid protein (PLP) (and its splice isoform DM20) and induction of the unfolded protein response. As opposed to previous studies of heterologous expression systems, we have analyzed PLP/DM20 trafficking in oligodendroglial cells, thereby revealing differences between PMD and SPG-2-associated PLP/DM20 isoforms. PLPA242Vand DM20A242V(jimpy-msdin mice), associated with seve…

Effect of transfection with PLP2 antisense oligonucleotides on gene expression of cadmium-treated MDA-MB231 breast cancer cells

2012

Emerging evidence indicates that cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity in human normal and pathological cells. We have already shown that exposure of MDA-MB231 breast cancer cells to 5 μM CdCl(2) for 96 h, apart from significantly affecting mitochondrial metabolism, induces modifications of the expression level of genes coding for members of stress response-, mitochondrial respiration-, MAP kinase-, NF-κB-, and apoptosis-related pathways. In the present study, we have expanded the knowledge on the biological effects of Cd-breast cancer cell interactions, indicating PLP2 (proteolipid protein-2) as a novel member of the…

Toward completion of the Earth’s proteome: an update a decade later

2017

Protein databases are steadily growing driven by the spread of new more efficient sequencing techniques. This growth is dominated by an increase in redundancy (homologous proteins with various degrees of sequence similarity) and by the incapability to process and curate sequence entries as fast as they are created. To understand these trends and aid bioinformatic resources that might be compromised by the increasing size of the protein sequence databases, we have created a less-redundant protein data set. In parallel, we analyzed the evolution of protein sequence databases in terms of size and redundancy. While the SwissProt database has decelerated its growth mostly because of a focus on i…

Assessing the low complexity of protein sequences via the low complexity triangle.

2020

Background Proteins with low complexity regions (LCRs) have atypical sequence and structural features. Their amino acid composition varies from the expected, determined proteome-wise, and they do not follow the rules of structural folding that prevail in globular regions. One way to characterize these regions is by assessing the repeatability of a sequence, that is, calculating the local propensity of a region to be part of a repeat. Results We combine two local measures of low complexity, repeatability (using the RES algorithm) and fraction of the most frequent amino acid, to evaluate different proteomes, datasets of protein regions with specific features, and individual cases of proteins…

Proteome-wide comparison between the amino acid composition of domains and linkers

2018

Objective Amino acid composition is a sequence feature that has been extensively used to characterize proteomes of many species and protein families. Yet the analysis of amino acid composition of protein domains and the linkers connecting them has received less attention. Here, we perform both a comprehensive full-proteome amino acid composition analysis and a similar analysis focusing on domains and linkers, to uncover domain- or linker-specific differential amino acid usage patterns. Results The amino acid composition in the 38 proteomes studied showcase the greater variability found in archaea and bacteria species compared to eukaryotes. When focusing on domains and linkers, we describe …

The skeleton of the staghorn coral Acropora millepora: molecular and structural characterization.

2014

15 pages; International audience; The scleractinian coral Acropora millepora is one of the most studied species from the Great Barrier Reef. This species has been used to understand evolutionary, immune and developmental processes in cnidarians. It has also been subject of several ecological studies in order to elucidate reef responses to environmental changes such as temperature rise and ocean acidification (OA). In these contexts, several nucleic acid resources were made available. When combined to a recent proteomic analysis of the coral skeletal organic matrix (SOM), they enabled the identification of several skeletal matrix proteins, making A. millepora into an emerging model for biomi…