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FEBS Journal

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https://www.readbyqxmd.com/read/29156487/evolution-and-molecular-mechanism-of-four-electron-reducing-ferredoxin-dependent-bilin-reductases-from-oceanic-phages
#1
Benjamin Ledermann, Meike Schwan, Johannes A Sommerkamp, Eckhard Hofmann, Oded Béjà, Nicole Frankenberg-Dinkel
Ferredoxin-dependent bilin reductases (FDBRs) are a class of enzymes reducing the heme metabolite biliverdin IXα (BV) to form open-chain tetrapyrroles used for light-perception and light-harvesting in photosynthetic organisms. Thus far, seven FDBR families have been identified, each catalyzing a distinct reaction and either transferring two or four electrons from ferredoxin onto the substrate. The newest addition to the family is PcyX, originally identified from metagenomics data derived from phage. Phylogenetically, PcyA is the closest relative catalyzing the reduction of BV to phycocyanobilin...
November 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29155505/phistc-protein-family-members-localize-to-different-sub-cellular-organelles-and-bind-plasmodium-falciparum-major-virulence-factor-pfemp-1
#2
Vikash Kumar, Jasweer Kaur, Amrit Pal Singh, Vineeta Singh, Anjali Bisht, Jiban Jyoti Panda, Prakash Chandra Mishra, Rachna Hora
Plasmodium falciparum (Pf) encodes a novel repertoire of exported protein family called as Plasmodium helical interspersed sub-telomeric (PHIST) that plays diverse roles in infected red blood cells (iRBCs), contributing to malaria pathogenesis. PHIST proteins are central to parasite biology, and modify human erythrocytes by executing interactions with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of PHISTc sub-family 'PFD1140w and PF11_0503', and compared our findings with a well characterized member 'PFI1780w'...
November 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29155493/the-crystal-structure-and-catalytic-mechanism-of-hydroxynitrile-lyase-from-passion-fruit-passiflora-edulis
#3
Fumihiro Motojima, Aem Nuylert, Yasuhisa Asano
Hydroxynitrile lyases (HNLs) are enzymes used in the synthesis of chiral cyanohydrins. The HNL from Passiflora edulis (PeHNL) is R-selective and is the smallest HNL known to date. The crystal structures of PeHNL and its C-terminal peptide depleted derivative were determined by molecular replacement method using the template structure of a heat stable protein, SP1, from Populus tremula at 2.8 Å and 1.8 Å resolution, respectively. PeHNL belongs to dimeric α+β barrel superfamily consisting of a central β-barrel in the middle of a dimer...
November 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29151277/mammalian-mitophagy-from-in-vitro-molecules-to-in-vivo-models
#4
REVIEW
Catherine E Rodger, Thomas G McWilliams, Ian G Ganley
The autophagic turnover of mitochondria, termed mitophagy, is thought to play an essential role in not only maintaining the health of the mitochondrial network, but also that of the cell and organism as a whole. We have come a long way in identifying the molecular components required for mitophagy through extensive in vitro work and cell line characterisation, yet the physiological significance and context of these pathways remains largely unexplored. This is highlighted by the recent development of new mouse models that have revealed a striking level of variation in mitophagy, even under normal conditions...
November 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29151266/crystal-structure-and-catalytic-characterization-of-the-dehydrogenase-reductase-sdr-family-member-4-dhrs4-from-caenorhabditis-elegans
#5
Michael Kisiela, Annette Faust, Bettina Ebert, Edmund Maser, Axel J Scheidig
The human dehydrogenase/reductase SDR family member 4 (DHRS4) is a tetrameric protein that is involved in the metabolism of several aromatic carbonyl compounds, steroids and bile acids. The only invertebrate DHRS4 that has been characterized to date is that from the model organism Caenorhabditis elegans. We have previously cloned and initially characterized this protein that was recently annotated as DHRS4_CAEEL in the UniProtKB database. Crystallization and X-ray diffraction studies of the full-length DHRS4_CAEEL protein in complex with diacetyl revealed its tetrameric structure and showed that two subunits are connected via an intermolecular disulfide bridge that is formed by N-terminal cysteine residues (Cys5) of each protein chain, which increases the enzymatic activity...
November 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29151265/cnn3-regulates-neural-tube-morphogenesis-and-neuronal-stem-cell-properties
#6
Dirk Junghans, Sebastian Herzog
Calponin 3 (Cnn3) is a member of the calponin family of actin binding molecules that is highly expressed in the mammalian brain and has been shown to control dendritic spine morphology, density and plasticity by regulating actin cytoskeletal reorganization and dynamics. However, little is known about the role of Cnn3 during embryonic development. In this study we analyzed mutant animals deficient in Cnn3 to gain a better understanding of its role in brain morphogenesis. Embryos lacking Cnn3 exhibited massive malformation of the developing brain including exoencephaly, closure defects at the rostral neural tube and strong enlargement of brain tissue...
November 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29150978/mice-lacking-a-functional-nmda-receptor-exhibit-social-subordination-in-a-group-housed-environment
#7
Waka Ujita, Ayako Kohyama-Koganeya, Nozomi Endo, Toki Saito, Hiroshi Oyama
Social dominance, in which an individual asserts control over others or benefits most after social conflict, has an influence on social behaviour. However, the mechanisms mediating social dominance remain unclear. Social dominance within social groups determines the distribution of rewards such as food and access to mating partners, which can act as reinforcers. In this study, we used the water competition test to determine whether mice were dominant or subordinate. We have previously reported that mice heterozygous for a missense mutation in Grin1 (Grin1(Rgsc174) ) showed altered social behaviour, with increased locomotor activity, novelty-seeking and anxiety...
November 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29150976/salt-bridge-interactions-within-the-%C3%AE-2-integrin-%C3%AE-7-helix-mediate-force-induced-binding-and-shear-resistance-ability
#8
Xiao Zhang, Linda Li, Ning Li, Xinyu Shu, Lüwen Zhou, Shouqin Lü, Shenbao Chen, Debin Mao, Mian Long
The functional performance of αI domain α7 helix in β2 integrin activation depends on the allostery of the α7 helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the α7 helix. Molecular Dynamics (MD) simulations for three β2 integrin members of LFA-1 (αL β2 ), Mac-1 (αM β2 ) and αx β2 indicated that the magnitude of the salt bridge interaction is related to the stability of the αI domain and the strength of the corresponding force-induced allostery...
November 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29148254/connecting-color-with-assembly-in-the-fluorescent-b-phycoerythrin-protein-complex
#9
Aneika C Leney, Aline Tschanz, Albert J R Heck
Phycoerythrin is the major light-harvesting pigment protein in red algae and is nowadays widely used as a fluorescent probe in biotechnological applications such as flow cytometry and immunofluorescence microscopy. In addition, it has had substantial economic impact due to its potential as a natural food colorant. However, knowledge on the precise molecular composition of phycoerythrin is limited. Here, we use a combination of high resolution native mass spectrometry (MS) and fluorescence spectroscopy to characterize the assembly properties of the B-phycoerythrin protein complex from Porphyridium cruentum...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29148236/emerging-roles-of-er-stress-in-the-aetiology-and-pathogenesis-of-alzheimer-s-disease
#10
REVIEW
Yannis Gerakis, Claudio Hetz
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synaptic dysfunction and accumulation of abnormal aggregates formed by amyloid-β peptides or phophorylated Tau proteins. Accumulating evidence suggests that alterations in the buffering capacity of the proteostasis network is a salient feature of AD. The endoplasmic reticulum (ER) is the main compartment involved in protein folding and secretion and is drastically affected in AD neurons. ER stress triggers the activation of the Unfolded Protein Response (UPR), a signal transduction pathway that enforces adaptive programs to recover homeostasis or trigger apoptosis of irreversibly damaged cells...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29148177/high-concentrations-of-gtp-induce-conformational-changes-in-the-essential-bacterial-gtpase-enga-and-enhance-its-binding-to-the-ribosome
#11
Catarina da Silveira Tomé, Anne-Emmanuelle Foucher, Jean-Michel Jault, Dominique Housset
EngA is a conserved bacterial GTPase involved in ribosome biogenesis. While essential in bacteria, EngA does not have any human ortholog and can thus be an interesting target for new antibacterial compounds. EngA is the only known GTPase bearing two G-domains, making unique its catalytic cycle and the induced modulation of its conformation and interaction with the ribosome. We have investigated nucleotide-induced conformational changes in EngA in order to unveil their role in ribosome binding. SAXS and limited proteolysis were used to probe EngA conformational changes, and revealed a change in protein structure and a distinct rate of proteolysis induced by GTP...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29143452/engineering-improved-variants-of-the-antifungal-peptide-histatin-5-with-reduced-susceptibility-to-candida-albicans-secreted-aspartic-proteases-and-enhanced-antimicrobial-potency
#12
Svetlana P Ikonomova, Parisa Moghaddam-Taaheri, Mary Ann Jabra-Rizk, Yan Wang, Amy J Karlsson
Candida albicans is an opportunistic fungal pathogen and a commensal organism that commonly colonizes mucosal surfaces, including those inside the human mouth. To help control C. albicans, human saliva contains the antifungal peptide histatin 5 (Hst-5), which has strong antifungal activity against C. albicans. However, the pathogen produces secreted aspartic proteases (Saps) that cleave Hst-5 at lysine residues and eliminate its antifungal properties. We designed variants of Hst-5 with its lysine residues substituted with arginine or leucine to evaluate the effect on proteolysis by Saps...
November 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29131550/innate-and-acquired-immune-surveillance-in-the-post-dissemination-phase-of-metastasis
#13
REVIEW
Hugo Gonzalez, Isabella Robles, Zena Werb
Metastasis is responsible for the majority of death in cancer patients. Of the different steps in the metastasis cascade, the post-dissemination phase is perhaps one of the least understood. Many factors, both from the disseminated tumor cells (DTCs) and the microenvironment, impact the success of the metastatic outgrowth. In this article, we discuss the interactions between colonizing cancer cells and immune cells in the period between vascular arrest in a secondary organ and metastatic outgrowth. We address the ambiguity in the findings of current research regarding the role of immune cells in regulating the metastatic microenvironment, and their hand in determining cancer cell fate...
November 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29131545/a-double-point-mutation-at-residues-ile14-and-val15-of-bcl-2-uncovers-a-role-for-bh4-domain-in-both-protein-stability-and-function
#14
Giovanni Monaco, Rita La Rovere, Spyridoula Karamanou, Kirsten Welkenhuyzen, Hristina Ivanova, Elien Vandermarliere, Marta Di Martile, Donatella Del Bufalo, Humbert De Smedt, Jan B Parys, Anastassios Economou, Geert Bultynck
B-cell lymphoma 2 (Bcl-2) protein is the archetype apoptosis suppressor protein. The N-terminal Bcl-2-homology 4 (BH4) domain of Bcl-2 is required for the anti-apoptotic function of this protein at the mitochondria and endoplasmic reticulum (ER). The involvement of the BH4 domain in Bcl-2's anti-apoptotic functions has been proposed based on Gly-based substitutions of the Ile14/Val15 amino acids, two hydrophobic residues located in the centre of Bcl-2's BH4 domain. Following this strategy, we recently showed that a BH4-domain-derived peptide in which Ile14 and Val15 have been replaced by Gly residues, was unable to dampen pro-apoptotic Ca(2+) -release events from the ER...
November 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29125686/neurophagy-the-phagocytosis-of-live-neurons-and-synapses-by-glia-contributes-to-brain-development-and-disease
#15
REVIEW
Anna Vilalta, Guy C Brown
It was previously thought that neurons were phagocytosed only when dead or dying. However, it is increasingly clear that viable synapses, dendrites, axons and/or neurons can be phagocytosed alive (defined here as "neurophagy"), and this may contribute to a wide range of developmental, physiological and pathological processes. Phagocytosis of live synapses, dendrites and axons by glia, contribute to experience-dependent sculpting of neuronal networks during development, but excessive phagocytosis of synapses may contribute to pathology in Alzheimer's disease, schizophrenia and aging...
November 10, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29121446/vbp1-represses-cancer-metastasis-by-enhancing-hif-1%C3%AE-degradation-induced-by-pvhl
#16
Ji Ae Kim, Da Kyung Choi, Jung Sun Min, Inho Kang, Jin Chul Kim, Semi Kim, Jeong Keun Ahn
VBP1 physically interacts with pVHL, an E3-ubiquitin ligase, which degrades HIF-1α in an oxygen-dependent manner. HIF-1 is a key regulator of adaptive responses to a lack of oxygen that controls glucose metabolism, angiogenesis, proliferation, invasion, and metastasis. However, the role of VBP1 in pVHL-mediated degradation of HIF-1α is not yet known. In this study, we show that VBP1 enhances the stability of pVHL and facilitates pVHL-mediated ubiquitination of HIF-1α. Furthermore, VBP1 suppresses HIF-1α-induced epithelial-mesenchymal transition in vitro and tumor metastasis in vivo...
November 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29117645/proteomic-profiling-of-tgfbi-null-mouse-corneas-reveals-only-minor-changes-in-matrix-composition-supportive-of-tgfbi-knockdown-as-therapy-against-tgfbi-linked-corneal-dystrophies
#17
Ebbe Toftgaard Poulsen, Kasper Runager, Nadia Sukusu Nielsen, Marie V Lukassen, Karen Thomsen, Paige Snider, Olga Simmons, Henrik Vorum, Simon J Conway, Jan J Enghild
TGFBIp is a constituent of the extracellular matrix in many human tissues including the cornea, where it is one of the most abundant proteins expressed. TGFBIp interacts with Type I, II, IV, VI and XII collagens as well as several members of the integrin family, suggesting it plays an important role in maintaining structural integrity and possibly corneal transparency as well. Significantly, more than 60 point mutations within the TGFBI gene have been reported to result in aberrant TGFBIp folding and aggregation in the cornea, resulting in severe visual impairment and blindness...
November 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29114997/in-vitro-modeling-of-hiv-proviral-activity-in-microglia
#18
Lee A Campbell, Christopher T Richie, Yajun Zhang, Emily J Heathward, Lamarque M Coke, Emily Y Park, Brandon K Harvey
Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection...
November 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29113027/detect-correct-retract-how-to-manage-incorrect-structural-models
#19
REVIEW
Alexander Wlodawer, Zbigniew Dauter, Przemyslaw J Porebski, Wladek Minor, Robyn Stanfield, Mariusz Jaskolski, Edwin Pozharski, Christian X Weichenberger, Bernhard Rupp
The massive technical and computational progress of biomolecular crystallography has generated some adverse side effects. Most crystal structure models, produced by crystallographers or well-trained structural biologists, constitute useful sources of information, but occasional extreme outliers remind us that the process of structure determination is not fail-safe. The occurrence of severe errors or gross misinterpretations raises fundamental questions: Why do such aberrations emerge in the first place? How did they evade the sophisticated validation procedures which often produce clear and dire warnings, and why were severe errors not noticed by the depositors themselves, their supervisors, referees, and editors? Once detected, what can be done to either correct, improve, or eliminate such models? How do incorrect models affect the underlying claims or biomedical hypotheses they were intended, but failed, to support? What is the long-range effect of the propagation of such errors? And finally, what mechanisms can be envisioned to restore the validity of the scientific record and, if necessary, retract publications that are clearly invalidated by the lack of experimental evidence? We suggest that cognitive bias and flawed epistemology are likely at the root of the problem...
November 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29106767/phagocyte-extracellular-matrix-crosstalk-empowers-tumour-development-and-dissemination
#20
REVIEW
Chen Varol, Irit Sagi
Phagocytes, such as tumour-associated macrophages (TAMs) and tumour-associated neutrophils (TANs), are abundant in the stroma of experimental and human tumours and are locally educated to mediate important biological functions that profoundly affect tumour initiation, growth and dissemination. Of considerable importance is the non- cellular component of the tumour microenvironment, namely - the extracellular matrix (ECM). This milieu is often overlooked due to its complexity and vast heterogeneity. Biophysical and biomechanical cues provided by the dynamically evolving tumourigenic ECM fundamentally modulate every behavioral facet of the cancer cells and of associated stromal cells...
November 6, 2017: FEBS Journal
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