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Biochemical Society Transactions

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https://www.readbyqxmd.com/read/28630139/functional-interfaces-between-ticam-2-tram-and-ticam-1-trif-in-tlr4-signaling
#1
REVIEW
Kenji Funami, Misako Matsumoto, Hiroyuki Oshiumi, Fuyuhiko Inagaki, Tsukasa Seya
Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS), produces pro-inflammatory cytokines and type I interferons, and associates with a trigger of endotoxin shock. TLR4 is interacted with a TIR domain-containing adaptor molecule-2 (TICAM-2)/TRAM [TRIF (TIR domain-containing adaptor-inducing interferon-β)-related adaptor molecule] via its Toll-interleukin-1 receptor homology (TIR) domain. TICAM-2 acts as a scaffold protein and activates TIR domain-containing adaptor molecule-1 (TICAM-1)/TRIF. According to the structural analysis by NMR, TICAM-2 interacts with TICAM-1 by the acidic amino acids motif, E87/D88/D89...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28630138/targeting-the-ras-palmitoylation-depalmitoylation-cycle-in-cancer
#2
REVIEW
David Tse Shen Lin, Nicholas G Davis, Elizabeth Conibear
The Ras proteins are well-known drivers of many cancers and thus represent attractive targets for the development of anticancer therapeutics. Inhibitors that disrupt the association of the Ras proteins with membranes by blocking the addition of the farnesyl lipid moiety to the Ras C-terminus failed in clinical trials. Here, we explore the possibility of targeting a second lipid modification, S-acylation, commonly referred to as palmitoylation, as a strategy to disrupt the membrane interaction of specific Ras isoforms...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28630137/structure-and-function-of-dhhc-protein-s-acyltransferases
#3
REVIEW
Colin D Gottlieb, Maurine E Linder
It has been estimated that 10% of the human genome encodes proteins that are fatty acylated at cysteine residues. The vast majority of these proteins are modified by members of the DHHC protein family, which carry out their enzymatic function on the cytoplasmic face of cell membranes. The biomedical importance of DHHC proteins is underscored by their association with human disease; unique and essential roles for DHHC proteins have been uncovered using DHHC-deficient mouse models. Accordingly, there is great interest in elucidating the molecular mechanisms that underlie DHHC protein function...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620046/role-of-escrt-component-hd-ptp-ptpn23-in-cancer
#4
REVIEW
Marie-Claude Gingras, Jalal M Kazan, Arnim Pause
Sustained cellular signalling originated from the receptors located at the plasma membrane is widely associated with cancer susceptibility. Endosomal sorting and degradation of the cell surface receptors is therefore crucial to preventing chronic downstream signalling and tumorigenesis. Since the Endosomal Sorting Complexes Required for Transport (ESCRT) controls these processes, ESCRT components were proposed to act as tumour suppressor genes. However, the bona fide role of ESCRT components in tumorigenesis has not been clearly demonstrated...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620045/fundamental-principles-of-vascular-network-topology
#5
REVIEW
Veronika S Kopylova, Stanislav E Boronovskiy, Yaroslav R Nartsissov
The vascular system is arguably the most important biological system in many organisms. Although the general principles of its architecture are simple, the growth of blood vessels occurs under extreme physical conditions. Optimization is an important aspect of the development of computational models of the vascular branching structures. This review surveys the approaches used to optimize the topology and estimate different geometrical parameters of the vascular system. The review is focused on optimizations using complex cost functions based on the minimum total energy principle and the relationship between the laws of growth and precise vascular network topology...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620044/let-there-be-light-how-to-use-photoswitchable-cross-linker-to-reprogram-proteins
#6
REVIEW
Daniel Hoersch
Azobenzene is a photo-isomerizing molecule whose end-to-end distance changes upon external illumination. When combined with site-specific reactive groups, it can be used as molecular tweezers to remote-control the structure and function of protein targets. The present study gives a brief overview over the rational design strategies that use an azobenzene-based photoswitchable cross-linker to engineer ON/OFF switches into functional proteins or to reprogram proteins for novel functions. The re-engineered proteins may be used as remote controls for cellular pathways, as light-gated drug delivery platforms or as light-powered machinery of synthetic cells and micro-scaled factories...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620043/mitochondrial-cytochrome-c-oxidase-catalysis-coupling-and-controversies
#7
REVIEW
Peter R Rich
Mitochondrial cytochrome c oxidase is a member of a diverse superfamily of haem-copper oxidases. Its mechanism of oxygen reduction is reviewed in terms of the cycle of catalytic intermediates and their likely chemical structures. This reaction cycle is coupled to the translocation of protons across the inner mitochondrial membrane in which it is located. The likely mechanism by which this occurs, derived in significant part from studies of bacterial homologues, is presented. These mechanisms of catalysis and coupling, together with current alternative proposals of underlying mechanisms, are critically reviewed...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620042/long-noncoding-rnas-lincs-between-human-health-and-disease
#8
REVIEW
Zhi Hao Kwok, Yvonne Tay
Long noncoding RNAs (lncRNAs) represent one of the largest classes of transcripts and are highly diverse in terms of characteristics and functions. Advances in high-throughput sequencing platforms have enabled the rapid discovery and identification of lncRNAs as key regulatory molecules involved in various cellular processes and their dysregulation in various human diseases. Here, we summarize the current knowledge of the functions and underlying mechanisms of lncRNA activity with a particular focus on cancer biology...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620041/a-standard-enabled-workflow-for-synthetic-biology
#9
REVIEW
Chris J Myers, Jacob Beal, Thomas E Gorochowski, Hiroyuki Kuwahara, Curtis Madsen, James Alastair McLaughlin, Göksel Mısırlı, Tramy Nguyen, Ernst Oberortner, Meher Samineni, Anil Wipat, Michael Zhang, Zach Zundel
A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620040/cell-free-synthetic-biology-for-in-vitro-prototype-engineering
#10
REVIEW
Simon J Moore, James T MacDonald, Paul S Freemont
Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620039/csbb-synthetic-biology-research-at-newcastle-university
#11
EDITORIAL
Angel Goñi-Moreno, Anil Wipat, Natalio Krasnogor
The Centre for Synthetic Biology and the Bioeconomy (CSBB) brings together a far-reaching multidisciplinary community across all Newcastle University's faculties - Medical Sciences, Science, Agriculture and Engineering, and Humanities, Arts and Social Sciences. The CSBB focuses on many different areas of Synthetic Biology, including bioprocessing, computational design and in vivo computation, as well as improving understanding of basic molecular machinery. Such breadth is supported by major national and international research funding, a range of industrial partners in the North East of England and beyond, as well as a large number of doctoral and post-doctoral researchers...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620038/appl1-is-a-multifunctional-endosomal-signaling-adaptor-protein
#12
REVIEW
Nicole L Diggins, Donna J Webb
Endosomal adaptor proteins are important regulators of signaling pathways underlying many biological processes. These adaptors can integrate signals from multiple pathways via localization to specific endosomal compartments, as well as through multiple protein-protein interactions. One such adaptor protein that has been implicated in regulating signaling pathways is the adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (APPL1). APPL1 localizes to a subset of Rab5-positive endosomes through its Bin-Amphiphysin-Rvs and PH domains, and it coordinates signaling pathways through its interaction with many signaling receptors and proteins through its PTB domain...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620037/the-more-the-merrier-high-throughput-single-molecule-techniques
#13
REVIEW
Flynn R Hill, Enrico Monachino, Antoine M van Oijen
The single-molecule approach seeks to understand molecular mechanisms by observing biomolecular processes at the level of individual molecules. These methods have led to a developing understanding that for many processes, a diversity of behaviours will be observed, representing a multitude of pathways. This realisation necessitates that an adequate number of observations are recorded to fully characterise this diversity. The requirement for large numbers of observations to adequately sample distributions, subpopulations, and rare events presents a significant challenge for single-molecule techniques, which by their nature do not typically provide very high throughput...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620036/substrate-selectivity-in-the-zdhhc-family-of-s-acyltransferases
#14
REVIEW
Kimon Lemonidis, Christine Salaun, Marianna Kouskou, Cinta Diez-Ardanuy, Luke H Chamberlain, Jennifer Greaves
S-acylation is a reversible lipid modification occurring on cysteine residues mediated by a family of membrane-bound 'zDHHC' enzymes. S-acylation predominantly results in anchoring of soluble proteins to membrane compartments or in the trafficking of membrane proteins to different compartments. Recent work has shown that although S-acylation of some proteins may involve very weak interactions with zDHHC enzymes, a pool of zDHHC enzymes exhibit strong and specific interactions with substrates, thereby recruiting them for S-acylation...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620035/molecular-interactions-shaping-the-tetraspanin-web
#15
REVIEW
Sjoerd J van Deventer, Vera-Marie E Dunlock, Annemiek B van Spriel
To facilitate the myriad of different (signaling) processes that take place at the plasma membrane, cells depend on a high degree of membrane protein organization. Important mediators of this organization are tetraspanin proteins. Tetraspanins interact laterally among themselves and with partner proteins to control the spatial organization of membrane proteins in large networks called the tetraspanin web. The molecular interactions underlying the formation of the tetraspanin web were hitherto mainly described based on their resistance to different detergents, a classification which does not necessarily correlate with functionality in the living cell...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620034/structural-insights-into-the-alternative-oxidases-are-all-oxidases-made-equal
#16
REVIEW
Benjamin May, Luke Young, Anthony L Moore
The alternative oxidases (AOXs) are ubiquinol-oxidoreductases that are members of the diiron carboxylate superfamily. They are not only ubiquitously distributed within the plant kingdom but also found in increasing numbers within the fungal, protist, animal and prokaryotic kingdoms. Although functions of AOXs are highly diverse in general, they tend to play key roles in thermogenesis, stress tolerance (through the management of radical oxygen species) and the maintenance of mitochondrial and cellular energy homeostasis...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620033/scissor-sisters-regulation-of-adam10-by-the-tspanc8-tetraspanins
#17
REVIEW
Alexandra L Matthews, Justyna Szyroka, Richard Collier, Peter J Noy, Michael G Tomlinson
A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane protein which is essential for embryonic development through activation of Notch proteins. ADAM10 regulates over 40 other transmembrane proteins and acts as a 'molecular scissor' by removing their extracellular regions. ADAM10 is also a receptor for α-toxin, a major virulence factor of Staphylococcus aureus Owing to the importance of its substrates, ADAM10 is a potential therapeutic target for cancer, neurodegenerative diseases such as Alzheimer's and prion diseases, bacterial infection and inflammatory diseases such as heart attack, stroke and asthma...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620032/a-moving-target-structure-and-disorder-in-pursuit-of-myc-inhibitors
#18
REVIEW
Richard Bayliss, Selena G Burgess, Eoin Leen, Mark W Richards
The Myc proteins comprise a family of ubiquitous regulators of gene expression implicated in over half of all human cancers. They interact with a large number of other proteins, such as transcription factors, chromatin-modifying enzymes and kinases. Remarkably, few of these interactions have been characterized structurally. This is at least in part due to the intrinsically disordered nature of Myc proteins, which adopt a defined conformation only in the presence of binding partners. Owing to this behaviour, crystallographic studies on Myc proteins have been limited to short fragments in complex with other proteins...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620031/tspan7-effector-of-actin-nucleation-required-for-dendritic-cell-mediated-transfer-of-hiv-1-to-t-cells
#19
REVIEW
Mickaël M Ménager
Dendritic cells (DCs) have essential roles in early detection of pathogens and activation of both innate and adaptive immune responses. Whereas human DCs are resistant to productive HIV-1 replication, they have a unique ability to take up virus and transmit it efficiently to T lymphocytes. By doing that, HIV-1 may evade, at least in part, the first line of defense of the immune system, exploiting DCs instead to facilitate rapid infection of a large pool of immune cells. While performing an shRNA screen in human primary monocyte-derived DCs, to gain insights into this cell biological process, we discovered the role played by tetraspanin-7 (TSPAN7)...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28620030/functions-of-protein-phosphatase-6-in-nf-%C3%AE%C2%BAb-signaling-and-in-lymphocytes
#20
REVIEW
Magdalena A Ziembik, Timothy P Bender, James M Larner, David L Brautigan
Protein phosphatase-6 (PP6) is a member of the PPP family of Ser/Thr phosphatases involved in intracellular signaling. PP6 is conserved among all eukaryotes, and genetics in model organisms indicates it has non-redundant functions relative to other PPP phosphatases. PP6 functions in association with conserved SAPS subunits and, in vertebrate species, forms heterotrimers with Ankrd subunits. Multiple studies have demonstrated how PP6 exerts negative control at different steps of nuclear factor kappaB signaling...
June 15, 2017: Biochemical Society Transactions
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