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Protein complex

Eva Asselmann, Johannes Hertel, Carsten-Oliver Schmidt, Georg Homuth, Matthias Nauck, Christiane A Pané-Farré, Beesdo-Baum Katja, Hans-Jörgen Grabe
BACKGROUND: It remains unresolved whether childhood adversities interact with genetic variation in regulator of G-protein signaling 2 (RGS2) rs4606 in predicting various anxiety and depressive disorders and whether diagnostic specificity exists in these interactions. METHODS: The genotype of RGS2 rs4606 was determined for N = 2,263 adults with European ancestry from the Study of Health in Pomerania. Lifetime anxiety and depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were assessed with the Munich Composite International Diagnostic Interview (DIA-X/M-CIDI)...
August 14, 2018: Depression and Anxiety
Jelle Slager, Rieza Aprianto, Jan-Willem Veening
A precise understanding of the genomic organization into transcriptional units and their regulation is essential for our comprehension of opportunistic human pathogens and how they cause disease. Using single-molecule real-time (PacBio) sequencing we unambiguously determined the genome sequence of Streptococcus pneumoniae strain D39 and revealed several inversions previously undetected by short-read sequencing. Significantly, a chromosomal inversion results in antigenic variation of PhtD, an important surface-exposed virulence factor...
August 13, 2018: Nucleic Acids Research
Dario Cocciadiferro, Bartolomeo Augello, Pasquelena De Nittis, Jiyuan Zhang, Barbara Mandriani, Natascia Malerba, Gabriella M Squeo, Alessandro Romano, Barbara Piccinni, Tiziano Verri, Lucia Micale, Laura Pasqualucci, Giuseppe Merla
Kabuki syndrome is a rare autosomal dominant condition characterized by facial features, various organs malformations, postnatal growth deficiency and intellectual disability. The discovery of frequent germline mutations in the histone methyltransferase KMT2D and the demethylase KDM6A revealed a causative role for histone modifiers in this disease. However, the role of missense mutations has remained unexplored. Here, we expanded the mutation spectrum of KMT2D and KDM6A in KS by identifying 37 new KMT2D sequence variants...
June 22, 2018: Human Molecular Genetics
Ya-Jun Zhai, Hui Huang, Jianhua Liu, Hua-Run Sun, Dandan He, Yu-Shan Pan, Gongzheng Hu
Background: Colistin has been used as the last therapeutic resort for treatment of MDR Gram-negative bacteria infections in humans. The two-component system CpxAR has been reported to contribute to the MDR of bacteria. There may be a more complex network mediated by CpxAR contributing to colistin susceptibility than previously understood. Methods: A series of AcrB or CpxR deletion mutants of a multidrug-susceptible standard strain of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) was constructed in our previous study...
August 10, 2018: Journal of Antimicrobial Chemotherapy
Samuel Wagner, Iwan Grin, Silke Malmsheimer, Nidhi Singh, Claudia E Torres-Vargas, Sibel Westerhausen
Virulence-associated type III secretion systems serve the injection of bacterial effector proteins into eukaryotic host cells. They are able to secrete a great diversity of substrate proteins in order to modulate host cell function, and have evolved to sense host cell contact and to inject their substrates through a translocon pore in the host cell membrane. T3SS substrates contain an N-terminal signal sequence and often also a chaperone-binding domain for cognate T3SS chaperones. These signals guide the substrates to the machine where substrates are unfolded and handed over to the secretion channel formed by the transmembrane domains of the export apparatus components and by the the needle filament...
August 9, 2018: FEMS Microbiology Letters
Jesper S Johansen, Darius Kavaliauskas, Shawn H Pfeil, Mickaël Blaise, Barry S Cooperman, Yale E Goldman, Søren S Thirup, Charlotte R Knudsen
According to the traditional view, GTPases act as molecular switches, which cycle between distinct 'on' and 'off' conformations bound to GTP and GDP, respectively. Translation elongation factor EF-Tu is a GTPase essential for prokaryotic protein synthesis. In its GTP-bound form, EF-Tu delivers aminoacylated tRNAs to the ribosome as a ternary complex. GTP hydrolysis is thought to cause the release of EF-Tu from aminoacyl-tRNA and the ribosome due to a dramatic conformational change following Pi release. Here, the crystal structure of Escherichia coli EF-Tu in complex with a non-hydrolysable GTP analogue (GDPNP) has been determined...
August 11, 2018: Nucleic Acids Research
Robert VanBuren, Ching Man Wai, Marivi Colle, Jie Wang, Shawn Sullivan, Jill M Bushakra, Ivan Liachko, Kelly J Vining, Michael Dossett, Chad E Finn, Rubina Jibran, David Chagné, Kevin Childs, Patrick P Edger, Todd C Mockler, Nahla V Bassil
Background: The fragmented nature of most draft plant genomes has hindered downstream gene discovery, trait mapping for breeding, and other functional genomics applications. There is a pressing need to improve or finish draft plant genome assemblies. Findings: Here we present a chromosome-scale assembly of the black raspberry genome using single-molecule real-time (SMRT) PacBio sequencing and Hi-C genome scaffolding. The updated V3 assembly has a contig N50 of 5...
August 9, 2018: GigaScience
Tong Cao, Jing Pan, Xiulian Li, Yanli He, Yifei Jiang, Yajing Chang, Qi Zhang, Ying Lan, Hua Wang, Wenjie Jiao, Zibin Tian, Lijuan Zhang
BACKGROUND/AIMS: The up-regulation of hepatocyte growth factor/receptor, HGF/Met, signal transduction is observed in most of human cancers. Specific heparan sulfate structures enhance the HGF/Met signaling at both cell and animal-based model systems. Biochemical studies indicate that heparan sulfate interacts with HGF and a natural occurring splicing variant NK1 of HGF with similar affinity. However, it is currently unknown if cell surface heparan sulfate binds to Met at physiological conditions and if specific cell surface heparan sulfate structures are required for effective HGF/Met or NK1/Met signaling...
August 14, 2018: Cellular Physiology and Biochemistry
Joanna Makowska, Krzysztof Żamojć, Dariusz Wyrzykowski, Wiesław Wiczk, Lech Chmurzyński
Steady-state and time-resolved fluorescence spectroscopy, UV spectrophotometry and isothermal titration calorimetry techniques were used to study the coordinating properties of the 17aa peptide fragment (D17) derived from the central part of the mouse formin binding protein (FBP28 with the PDB code: 1E0L) towards Cu2+ ions. All the measurements were run in the 2-(N-morpholino)ethanesulfonic acid buffer (20 mM, pH 6.0). Under experimental conditions the formation of the 1:1 complex of Cu2+ ions with D17 is an entropy-driven process...
August 7, 2018: Biophysical Chemistry
Charles T Anderson
Assembly of polysaccharide-based walls by plant cells involves the rapid synthesis, trafficking, and deposition of complex biopolymers, but how these events are controlled and coordinated to achieve a strong, resilient extracellular matrix has remained obscure for decades. Recent quantitative analyses of fluorescence microscopy data have revealed details of the trafficking and synthetic activity of cellulose synthases, and new methods for labeling matrix polymers have unveiled aspects of their regulated deposition in the wall...
August 11, 2018: Current Opinion in Plant Biology
Sitai Liang, Edward A Medina, Boajie Li, Samy L Habib
Loss of Von Hippel-Lindau (VHL) in renal carcinoma cells results in up regulation of the activity of Hypoxia-Inducible Factor (HIF-α), a major transcription factor involved in kidney cancer. Rapamycin as mTOR inhibitor and 5-aminoimidazole-4-carboxamide (AICA)-riboside (AICAR) as AMPK activator are separately used to treat cancer patients. In the current study, the possible additive effect of drug combinations in reducing kidney tumorigenesis was investigated. Treatment with drug combinations significantly decreased cell proliferation, increased cell apoptosis, and abolished Akt phosphorylation and HIF-2α expression in RCC cells, including primary cells isolated from kidney cancer patients...
August 14, 2018: Molecular Oncology
Sanam Sane, Andre Hafner, Rekha Srinivasan, Daniall Masood, John L Slunecka, Collin J Noldner, Alex D Hanson, Taylor Kruisselbrink, Xuejun Wang, Yiyang Wang, Jun Yin, Khosrow Rezvani
Overexpression of oncoproteins is a major cause of treatment failure using current chemotherapeutic drugs. Drug-induced degradation of oncoproteins is feasible and can improve clinical outcomes in diverse types of cancers. Mortalin-2 (mot-2) is a dominant oncoprotein in several tumors, including colorectal cancer (CRC). In addition to inactivating the p53 tumor suppressor protein, mot-2 enhances tumor cell invasion and migration. Thus, mot-2 is considered a potential therapeutic target in several cancer types...
August 14, 2018: Molecular Oncology
Janine H Peterson, Sunyia Hussain, Harris D Bernstein
Although the barrel assembly machinery (Bam) complex has been shown to facilitate the insertion of β barrel proteins into the bacterial outer membrane (OM), the stage at which β barrels fold is unknown. Here we describe insights into β barrel assembly that emerged from an analysis of a member of the autotransporter family of OM proteins (EspP) in E. coli. EspP contains an extracellular "passenger" domain that is translocated across the OM and then released from the covalently linked β barrel domain in an intra-barrel cleavage reaction...
August 14, 2018: Molecular Microbiology
Eva Johanna Reschka, Steffen Nordzieke, Oliver Valerius, Gerhard H Braus, Stefanie Pöggeler
The STRIPAK complex is involved in growth, cell fusion, development, and signaling pathways, and thus malfunctions in the human STRIPAK complex often result in severe neuronal diseases and cancer. Despite the high degree of general conservation throughout the complex, several STRIPAK complex-associated small coiled-coil proteins of animals and yeasts are not conserved across species. As there are no data for filamentous ascomycetes, we addressed this through affinity purification with HA-tagged striatin ortholog PRO11 in Sordaria macrospora...
August 14, 2018: Molecular Microbiology
Matthew S Proctor, Jack W Chidgey, Mahendra K Shukla, Philip J Jackson, Roman Sobotka, C Neil Hunter, Andrew Hitchcock
In the model cyanobacterium Synechocystis sp. PCC 6803, the terminal enzyme of chlorophyll biosynthesis, chlorophyll synthase (ChlG), forms a complex with high-light-inducible proteins, the photosystem II assembly factor Ycf39, and the YidC/Alb3/OxaI membrane insertase, coordinating chlorophyll delivery with co-translational insertion of nascent photosystem polypeptides into the membrane. To gain insight into the ubiquity of this assembly complex in higher photosynthetic organisms, we produced functional foreign chlorophyll synthases in a cyanobacterial host...
August 14, 2018: FEBS Letters
Gavriel D Kohlberg, Ryan T Demmer, Anil K Lalwani
OBJECTIVE: We investigated the hypothesis that childhood obesity is a risk factor for sensorineural hearing loss (SNHL) independent of other metabolic risk factors. STUDY DESIGN: A complex, multistage, stratified geographic area design for collecting representative data from noninstitutionalized US population. METHODS: A total of 5,638 adolescents between age 12 and 19 from the NHANES database (2005-2010) were studied. Subjects with body mass index >= 95th percentile were classified as obese...
August 13, 2018: Otology & Neurotology
Cameron McDonald-Hyman, James T Muller, Michael Loschi, Govindarajan Thangavelu, Asim Saha, Sudha Kumari, Dawn K Reichenbach, Michelle J Smith, Guoan Zhang, Brent H Koehn, Jiqiang Lin, Jason S Mitchell, Brian T Fife, Angela Panoskaltsis-Mortari, Colby J Feser, Andrew Kemal Kirchmeier, Mark J Osborn, Keli L Hippen, Ameeta Kelekar, Jonathan S Serody, Laurence A Turka, David H Munn, Hongbo Chi, Thomas A Neubert, Michael L Dustin, Bruce R Blazar
Regulatory T-cells (Treg) are critical for maintaining immune homeostasis. However, current Treg immunotherapies do not optimally treat inflammatory diseases in patients. Understanding the cellular processes that control Treg function may allow for the augmentation of therapeutic efficacy. In contrast to activated conventional T-cells, where protein kinase C-θ (PKC-θ) localizes to the contact-point between T-cells and antigen-presenting cells, in human and mouse Treg, PKC-θ localizes to the opposite end of the cell in the distal pole complex (DPC)...
August 14, 2018: Journal of Clinical Investigation
Ivana Domljanovic, Anders Højgaard Hansen, Lykke H Hansen, Janne Kudsk Klitgaard, Maria Taskova, Kira Astakhova
Synthetic oligonucleotides, their complexes and conjugates with other biomolecules represent valuable research tools and therapeutic agents. In spite of growing applications in basic research and clinical science, only few studies have addressed the issue of such compounds' stability in biological media. Herein, we studied the stability of two therapeutically relevant oligonucleotide probes in simulated biofluids; the 21 nucleotide-long DNA/locked nucleic acid oligonucleotide ON targeted toward cancer-associated BRAF V600E mutation, and a longer DNA analog (TTC) originating from BRAF gene...
August 14, 2018: Nucleic Acid Therapeutics
Christian Beck, Marco Grimaldo, Felix Roosen-Runge, Michal Katharina Braun, Fajun Zhang, Frank Schreiber, Tilo Seydel
Protein diffusion is not only an important process ensuring biological function, but can also be used as a probe to obtain information on structural properties of protein assemblies in liquid solutions. Here, we explore the oligomerization state of ovalbumin at high protein concentrations by means of its short-time self-diffusion. We employ high-resolution incoherent quasi-elastic neutron scattering to access the self-diffusion on nanosecond time scales, on which interparticle contacts are not altered. Our results indicate that ovalbumin in aqueous (D2 O) solutions occurs in increasingly large assemblies of its monomeric subunits with rising protein concentration...
August 14, 2018: Journal of Physical Chemistry. B
Farhad Ramezanghorbani, Ping Lin, Coray M Colina
Increasing demand for hybrid materials that merge the synthetic and biological areas in drug industries requires in-depth knowledge of the individual components and their contributions to these complexes. Coarse-grained (CG) models developed for proteins and polymers exist, yet there is a lack of understanding of the cross interactions when these two groups of materials integrate to build a complex. In this work, we characterized the nonbonded interactions between poly(ethylene glycol) (PEG) and amino acids in a Martini CG model utilizing state-of-the-art quantum mechanics calculations of interaction energies...
August 14, 2018: Journal of Physical Chemistry. B
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