Search results for "sequence"
showing 10 items of 4987 documents
A motif-independent metric for DNA sequence specificity
2011
Abstract Background Genome-wide mapping of protein-DNA interactions has been widely used to investigate biological functions of the genome. An important question is to what extent such interactions are regulated at the DNA sequence level. However, current investigation is hampered by the lack of computational methods for systematic evaluating sequence specificity. Results We present a simple, unbiased quantitative measure for DNA sequence specificity called the Motif Independent Measure (MIM). By analyzing both simulated and real experimental data, we found that the MIM measure can be used to detect sequence specificity independent of presence of transcription factor (TF) binding motifs. We…
Electrochemical probe for the monitoring of DNA-protein interactions.
2010
Self-assembly of thiol-terminated oligonucleotides on gold substrates provides a convenient way for DNA-functionalized surfaces. Here we describe the development of an electrochemical assay for the detection of DNA-protein interactions based on the modification of the electrochemical response of methylene blue (MB) intercalated in the DNA strands. Using a functionalized electrode with double stranded DNA carrying T3 RNA polymerase binding sequence, we show a substantial attenuation of the current upon the DNA-protein interaction. Moreover, a Langmuir binding isotherm for T3 RNA polymerase (T3 Pol) gives a dissociation constant K(D) equal to 0.46+/-0.23 microM. Such value is 100 times lower …
The rise of the middle author: Investigating collaboration and division of labor in biomedical research using partial alphabetical authorship
2017
Contemporary biomedical research is performed by increasingly large teams. Consequently, an increasingly large number of individuals are being listed as authors in the bylines, which complicates the proper attribution of credit and responsibility to individual authors. Typically, more importance is given to the first and last authors, while it is assumed that the others (the middle authors) have made smaller contributions. However, this may not properly reflect the actual division of labor because some authors other than the first and last may have made major contributions. In practice, research teams may differentiate the main contributors from the rest by using partial alphabetical author…
Phosphorylation of serine residues is fundamental for the calcium-binding ability of Orchestin, a soluble matrix protein from crustacean calcium stor…
2003
International audience; Orchestia cavimana is a terrestrial crustacean, which cyclically stores calcium in diverticula of the midgut, in the form of calcified amorphous concretions. These concretions are associated with a proteinaceous matrix, the main constituent of the soluble matrix is Orchestin, an acidic calcium-binding protein [Testenière et al., Biochem. J. 361 (2002) 327-335]. In the present paper, we clearly demonstrate that Orchestin is phosphorylated on serine and tyrosine residues, but that calcium binding only occurs via the phosphoserine residues. To our knowledge, this is the first example of an invertebrate mineralization for which a post-translational modification is clearl…
Hydrophobic mismatch of mobile transmembrane helices: Merging theory and experiments
2012
Abstract Hydrophobic mismatch still represents a puzzle for transmembrane peptides, despite the apparent simplicity of this concept and its demonstrated validity in natural membranes. Using a wealth of available experimental 2 H NMR data, we provide here a comprehensive explanation of the orientation and dynamics of model peptides in lipid bilayers, which shows how they can adapt to membranes of different thickness. The orientational adjustment of transmembrane α-helices can be understood as the result of a competition between the thermodynamically unfavorable lipid repacking associated with peptide tilting and the optimization of peptide/membrane hydrophobic coupling. In the positive misma…
Membrane topology of gp41 and amyloid precursor protein: Interfering transmembrane interactions as potential targets for HIV and Alzheimer treatment
2009
AbstractThe amyloid precursor protein (APP), that plays a critical role in the development of senile plaques in Alzheimer disease (AD), and the gp41 envelope protein of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), are single-spanning type-1 transmembrane (TM) glycoproteins with the ability to form homo-oligomers. In this review we describe similarities, both in structural terms and sequence determinants of their TM and juxtamembrane regions. The TM domains are essential not only for anchoring the proteins in membranes but also have functional roles. Both TM segments contain GxxxG motifs that drive TM associations within the li…
Phosphorylation of cytochromes P450: First discovery of a posttranslational modification of a drug-metabolizing enzyme
2005
Cytochromes P450 (CYP) are important components of xenobiotic-metabolizing monooxygenases (CYP-dependent monooxygenases). Their regulation by induction, most commonly by transcriptional activation, mediated by xenobiotics, normally substrates of the corresponding CYP, is well known and has been widely studied. Our team has discovered an additional important regulation of xenobiotic-metabolizing CYPs pertaining to posttranslational modification by phosphorylation. Individual CYPs are phosphorylated by different protein kinases, leading to CYP isoenzyme-selective changes in the metabolism of individual substrates and consequent drastic changes in the control of genotoxic metabolites. Best stu…
Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas
2007
AbstractIntegrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them w…
Stitching proteins into membranes, not sew simple
2014
Abstract Most integral membrane proteins located within the endomembrane system of eukaryotic cells are first assembled co-translationally into the endoplasmic reticulum (ER) before being sorted and trafficked to other organelles. The assembly of membrane proteins is mediated by the ER translocon, which allows passage of lumenal domains through and lateral integration of transmembrane (TM) domains into the ER membrane. It may be convenient to imagine multi-TM domain containing membrane proteins being assembled by inserting their first TM domain in the correct orientation, with subsequent TM domains inserting with alternating orientations. However a simple threading model of assembly, with s…
Insertion and Topology of a Plant Viral Movement Protein in the Endoplasmic Reticulum Membrane
2002
Virus-encoded movement proteins (MPs) mediate cell-to-cell spread of viral RNA through plant membranous intercellular connections, the plasmodesmata. The molecular pathway by which MPs interact with viral genomes and target plasmodesmata channels is largely unknown. The 9-kDa MP from carnation mottle carmovirus (CarMV) contains two potential transmembrane domains. To explore the possibility that this protein is in fact an intrinsic membrane protein, we have investigated its insertion into the endoplasmic reticulum membrane. By using in vitro translation in the presence of dog pancreas microsomes, we demonstrate that CarMV p9 inserts into the endoplasmic reticulum without the aid of any addi…