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Coralie Di Scala, Jacques Fantini, Nouara Yahi, Francisco J Barrantes, Henri Chahinian
Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid. The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid. In this review, we first analyze the conformational flexibility of anandamide in aqueous and membrane phases. We next study the interaction of the neurotransmitter with membrane lipids and discuss the molecular basis of the unexpected selectivity of anandamide for cholesterol and ceramide from among other membrane lipids...
May 22, 2018: Biomolecules
Stephan Block
The capability of lipid bilayers to exhibit fluid-phase behavior is a fascinating property, which enables, for example, membrane-associated components, such as lipids (domains) and transmembrane proteins, to diffuse within the membrane. These diffusion processes are of paramount importance for cells, as they are for example involved in cell signaling processes or the recycling of membrane components, but also for recently developed analytical approaches, which use differences in the mobility for certain analytical purposes, such as in-membrane purification of membrane proteins or the analysis of multivalent interactions...
May 22, 2018: Biomolecules
Gergő Fülöp, Mario Brameshuber, Andreas M Arnold, Gerhard J Schütz, Eva Sevcsik
The organization and dynamics of proteins and lipids in the plasma membrane, and their role in membrane functionality, have been subject of a long-lasting debate. Specifically, it is unclear to what extent membrane proteins are affected by their immediate lipid environment and vice versa. Studies on model membranes and plasma membrane vesicles indicated preferences of proteins for lipid phases characterized by different acyl chain order; however, whether such phases do indeed exist in live cells is still not known...
May 17, 2018: Biomolecules
Athina Andrea, Natalia Molchanova, Håvard Jenssen
Bacterial biofilms pose a major threat to public health, as they are associated with at least two thirds of all infections. They are highly resilient and render conventional antibiotics inefficient. As a part of the innate immune system, antimicrobial peptides have drawn attention within the last decades, as some of them are able to eradicate biofilms at sub-minimum inhibitory concentration (MIC) levels. However, peptides possess a number of disadvantages, such as susceptibility to proteolytic degradation, pH and/or salinity-dependent activity and loss of activity due to binding to serum proteins...
May 16, 2018: Biomolecules
Muhammad Imran, Odile Sergent, Arnaud Tête, Isabelle Gallais, Martine Chevanne, Dominique Lagadic-Gossmann, Normand Podechard
The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes an important public health concern worldwide. Including obesity, numerous risk factors of NAFLD such as benzo[a]pyrene (B[a]P) and ethanol have been identified as modifying the physicochemical properties of the plasma membrane in vitro thus causing membrane remodeling-changes in membrane fluidity and lipid-raft characteristics. In this study, the possible involvement of membrane remodeling in the in vivo progression of steatosis to a steatohepatitis-like state upon co-exposure to B[a]P and ethanol was tested in obese zebrafish larvae...
May 14, 2018: Biomolecules
Anna Lappala, Wataru Nishima, Jacob Miner, Paul Fenimore, Will Fischer, Peter Hraber, Ming Zhang, Benjamin McMahon, Chang-Shung Tung
Membrane fusion proteins are responsible for viral entry into host cells—a crucial first step in viral infection. These proteins undergo large conformational changes from pre-fusion to fusion-initiation structures, and, despite differences in viral genomes and disease etiology, many fusion proteins are arranged as trimers. Structural information for both pre-fusion and fusion-initiation states is critical for understanding virus neutralization by the host immune system. In the case of Ebola virus glycoprotein (EBOV GP) and Zika virus envelope protein (ZIKV E), pre-fusion state structures have been identified experimentally, but only partial structures of fusion-initiation states have been described...
May 10, 2018: Biomolecules
Jonathan J Chen, Lyndsey N Schmucker, Donald P Visco
When excessively activated, C1 is insufficiently regulated, which results in tissue damage. Such tissue damage causes the complement system to become further activated to remove the resulting tissue damage, and a vicious cycle of activation/tissue damage occurs. Current Food and Drug Administration approved treatments include supplemental recombinant C1 inhibitor, but these are extremely costly and a more economical solution is desired. In our work, we have utilized an existing data set of 136 compounds that have been previously tested for activity against C1...
May 7, 2018: Biomolecules
Sujan Ghimire, Pumtiwitt C McCarthy
Heavy metal pollution of water is a significant environmental and public health concern. Current biological strategies for heavy metal removal from water are performed using microbial biopolymers, including polysaccharides, that are already fully formed. This creates limitations in adapting polysaccharides to increase binding affinity for specific metals. We propose that altering the specificity of polysaccharide-producing enzymes could be beneficial to improving metal capture by modified polysaccharides. We assess binding of Cu2+ and Pb2+ metal cations to Neisseria meningitidis -type polysaccharides...
May 5, 2018: Biomolecules
Christopher Francklyn, Herve Roy, Rebecca Alexander
The 11th IUBMB Focused Meeting on Aminoacyl-tRNA Synthetases was held in Clearwater Beach, Florida from 29 October⁻2 November 2017, with the aim of presenting the latest research on these enzymes and promoting interchange among aminoacyl-tRNA synthetase (ARS) researchers. Topics covered in the meeting included many areas of investigation, including ARS evolution, mechanism, editing functions, biology in prokaryotic and eukaryotic cells and their organelles, their roles in human diseases, and their application to problems in emerging areas of synthetic biology...
May 1, 2018: Biomolecules
Sophie L Mumford, Benjamin P Towler, Amy L Pashler, Onur Gilleard, Yella Martin, Sarah F Newbury
Effective management of melanoma depends heavily on early diagnosis. When detected in early non-metastatic stages, melanoma is almost 100% curable by surgical resection, however when detected in late metastatic stages III and IV, 5-year survival rates drop to ~50% and 10⁻25%, respectively, due to limited efficacy of current treatment options. This presents a pressing need to identify biomarkers that can detect patients at high risk of recurrence and progression to metastatic disease, which will allow for early intervention and survival benefit...
April 26, 2018: Biomolecules
Emeline Tanguy, Nawal Kassas, Nicolas Vitale
Cellular membranes are composed of thousands of different lipids usually maintained within a narrow range of concentrations. In addition to their well-known structural and metabolic roles, signaling functions for many lipids have also emerged over the last two decades. The latter largely depend on the ability of particular classes of lipids to interact specifically with a great variety of proteins and to regulate their localization and activity. Among these lipids, phosphatidic acid (PA) plays a unique role in a large repertoire of cellular activities, most likely in relation to its unique biophysical properties...
April 23, 2018: Biomolecules
Mauricio Arias, Kathlyn B Piga, M Eric Hyndman, Hans J Vogel
Antimicrobial peptides (AMPs) constitute a promising alternative for the development of new antibiotics that could potentially counteract the growing number of antibiotic-resistant bacteria. However, the AMP structure⁻function relationships remain unclear and detailed studies are still necessary. The positively charged amino acid residues (Arg and Lys) play a crucial role in the activity of most AMPs due to the promotion of electrostatic interactions between the peptides and bacterial membranes. In this work we have analyzed the antimicrobial and structural properties of several Trp-rich AMPs containing exclusively either Arg or Lys as the positively charged residues...
April 19, 2018: Biomolecules
Arnaud Marquette, Burkhard Bechinger
Biophysical and structural investigations are presented with a focus on the membrane lipid interactions of cationic linear antibiotic peptides such as magainin, PGLa, LL37, and melittin. Observations made with these peptides are distinct as seen from data obtained with the hydrophobic peptide alamethicin. The cationic amphipathic peptides predominantly adopt membrane alignments parallel to the bilayer surface; thus the distribution of polar and non-polar side chains of the amphipathic helices mirror the environmental changes at the membrane interface...
April 18, 2018: Biomolecules
Saleem A Banihani, Khawla F Abu-Alia, Omar F Khabour, Karem H Alzoubi
Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disorder. It is characterized by an inappropriate skin barrier function, allergen sensitization, and recurrent skin infections. Resistin is an adipokine expressed mainly in macrophages and monocytes; it has a role in the inflammatory process and is associated with multiple inflammatory human diseases; however, only few studies linked resistin to atopic dermatitis. This study tested the association between G>A (rs3745367) and C>T (rs3219177) single nucleotide polymorphisms (SNPs) of the RETN gene with atopic dermatitis...
March 27, 2018: Biomolecules
Kusum K Kharbanda, Martin J J Ronis, Colin T Shearn, Dennis R Petersen, Samir Zakhari, Dennis R Warner, Ariel E Feldstein, Craig J McClain, Irina A Kirpich
The symposium, "Role of Nutrition in Alcoholic Liver Disease", was held at the European Society for Biomedical Research on Alcoholism Congress on 9 October 2017 in Crete, Greece. The goal of the symposium was to highlight recent advances and developments in the field of alcohol and nutrition. The symposium was focused on experimental and clinical aspects in relation to the role of different types of dietary nutrients and malnutrition in the pathogenesis of alcoholic liver disease (ALD). The following is a summary of key research presented at this session...
March 26, 2018: Biomolecules
Patience Chatukuta, Tshegofatso B Dikobe, David T Kawadza, Katlego S Sehlabane, Mutsa M Takundwa, Aloysius Wong, Chris Gehring, Oziniel Ruzvidzo
Adenylate cyclases (ACs), much like guanylate cyclases (GCs), are increasingly recognized as essential parts of many plant processes including biotic and abiotic stress responses. In order to identify novel ACs, we have applied a search motif derived from experimentally tested GCs and identified a number of Arabidopsis thaliana candidates including a clathrin assembly protein (AT1G68110; AtClAP). AtClAP contains a catalytic centre that can complement the AC-deficient mutant cya A in E. coli , and a recombinant AtClAP fragment (AtClAP261-379 ) can produce cyclic adenosine 3',5' monophosphate (cAMP) from adenosine triphosphate (ATP) in vitro...
March 23, 2018: Biomolecules
Maria Mrakovcic, Leopold F Fröhlich
Autophagy is an indispensable mechanism of the eukaryotic cell, facilitating the removal and renewal of cellular components and thereby balancing the cell's energy consumption and homeostasis. Deregulation of autophagy is now regarded as one of the characteristic key features contributing to the development of tumors. In recent years, the suppression of autophagy in combination with chemotherapeutic treatment has been approached as a novel therapy in cancer treatment. However, depending on the type of cancer and context, interference with the autophagic machinery can either promote or disrupt tumorigenesis...
March 21, 2018: Biomolecules
Milagros Castellanos, Almudena Torres-Pardo, Rosa Rodríguez-Pérez, María Gasset
Acid proteins capable of nucleating Ca2+ and displaying aggregation capacity play key roles in the formation of calcium carbonate biominerals. The helix-loop helix EF-hands are the most common Ca2+ -binding motifs in proteins. Calcium is bound by the loop region. These motifs are found in many proteins that are regulated by calcium. Gad m 1, an Atlantic cod β-parvalbumin isoform, is a monomeric EF-hand protein that acts as a Ca2+ buffer in fish muscle; the neutral and acid apo-forms of this protein can form amyloids...
March 20, 2018: Biomolecules
Hongjian Li, Jiangjun Peng, Yee Leung, Kwong-Sak Leung, Man-Hon Wong, Gang Lu, Pedro J Ballester
It has recently been claimed that the outstanding performance of machine-learning scoring functions (SFs) is exclusively due to the presence of training complexes with highly similar proteins to those in the test set. Here, we revisit this question using 24 similarity-based training sets, a widely used test set, and four SFs. Three of these SFs employ machine learning instead of the classical linear regression approach of the fourth SF (X-Score which has the best test set performance out of 16 classical SFs)...
March 14, 2018: Biomolecules
Katherine Wood, Michael Tellier, Shona Murphy
The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79). H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation...
February 27, 2018: Biomolecules
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