- Journal article
Authors : Hendler, Adi; Akiva, Eyal; Sandhu, Mahakaran (2020) - Many enzymes that catalyze protein post-translational modifications (PTM) can specifically modify multiple target proteins. However, little is known regarding the molecular basis and evolution of multi-specificity in these enzymes. Here, we used bioinformatics and experimental approaches to investigate the molecular basis and evolution of multi-specificity in the sirtuin-1 (SIRT1) deacetylase. Guided by bioinformatics analysis of SIRT1 orthologues and substrates, we identified and&#x...
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- Journal article
Authors : Sgrignani, Jacopo; Cecchinato, Valentina; Fassi, Enrico M.A (2020) - During inflammatory reactions, the production and release of chemotactic factors guide the recruitment of selective leukocyte subpopulations. HMGB1 and the chemokine CXCL12, both released in the microenvironment, form a heterocomplex, which exclusively acts on the chemokine receptor CXCR4, enhancing cell migration and, in some pathological conditions such as Rheumatoid Arthritis, exacerbating the immune response. An excessive cell influx at the inflammatory site can be ...
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- Journal article
Authors : Sun, Kuanxiang; Tian, Wanli; Liu, Wenjing (2020) - PS flippase (P4-ATPase) transports PS from the outer to the inner leaflet of the lipid bilayer in the membrane to maintain PS asymmetry, which is important for biological activity of the cell. ATP11A is expressed in multiple tissues and plays a role in myotube formation. However, detailed cellular function of ATP11A remains elusive. Mutation analysis revealed that I91, L308 and E897 residues in ATP8A2 are important for flippase activity. In...
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- Journal article
Authors : Modenutti, Carlos P; Capurro, Juan I. Blanco; Ibba, Roberta (2020) - UDP-glucose:glycoprotein glucosyltransferase (UGGT) is the only known glycoprotein folding quality control checkpoint in the eukaryotic glycoprotein secretory pathway. When the enzyme detects a misfolded glycoprotein in the Endoplasmic Reticulum (ER), it dispatches it for ER retention by re-glucosylating it on one of its N-linked glycans. Recent crystal structures of a fungal UGGT have suggested the enzyme is conformationally mobile. Here, a negative stain electron mic...
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- Journal article
Authors : Klooster, Joury S van ‘t; Cheng, Tan-Yun; Sikkema, Hendrik R (2020) - The yeast plasma membrane is segregated into domains: the Micro-Compartment-of-Can1 (MCC) and Pma1 (MCP) have a different protein composition, but their lipid composition is largely unknown. We extracted proteins residing in these microdomains via stoichiometric capture of lipids and proteins in styrene-maleic-acid-lipid-particles (SMALPs). We purified SMALPs by affinity chromatography and quantitatively analyzed the lipids by mass spectrometry and their role in transporter func...
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- Journal article
Authors : Koch, Amanda; Aguilera, Luis; Morisaki, Tatsuya (2020) - Viruses use IRES sequences within their RNA to hijack translation machinery and thereby rapidly replicate in host cells. While this process has been extensively studied in bulk assays, the dynamics of hijacking at the single-molecule level remain unexplored in living cells. To achieve this, we developed a bicistronic biosensor encoding complementary repeat epitopes in two ORFs, one translated in a Cap-dependent manner and the other translated in an ...
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- Journal article
Authors : Barra, Angélica Luana C; Dantas, Lívia de Oliveira C; Morão, Luana Galvão (2020) - The antibiotic resistance is a worldwide concern that requires a concerted action from physicians, patients, governmental agencies and academia to prevent infections and the spread of resistance, to track resistant bacteria, to improve the use of current antibiotics and to develop new antibiotics. Despite the efforts spent so far, the current antibiotics in the market are restricted to only five general targets/pathways highlighting the need for basic&#x...
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- Journal article
Authors : Madlung, Johannes; Bansal, Prashali; Schaaf, Kristina (2020) - During Drosophila oogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from whole Drosophila ovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and ...
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- Journal article
Authors : Ngo, Tony; Stephens, Bryan S; Gustavsson, Martin (2020) - Reporting the discovery of the geometry of the complex between full-length CXCR4, a prototypical CXC receptor and driver of cancer metastasis, and its endogenous ligand CXCL12. By comprehensive disulfide crosslinking, we establish the existence and the structure of a novel interface between the CXCR4 distal N-terminus and CXCL12 β1-strand, while also recapitulating earlier findings from NMR, modeling and crystallography of homologous receptors. A crosslinking-informed ...
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- Journal article
Authors : Mrozowich, Tyler; Henrickson, Amy; Demeler, Borries (2020) - Viral infections are responsible for numerous deaths worldwide. Flaviviruses, which contain RNA as their genetic material, are one of the most pathogenic families of viruses. There is an increasing amount of evidence suggesting that their 5’ and 3’ non-coding terminal regions are critical for their survival. In this study, the 5’ and 3’ terminal regions of Murray Valley Encephalitis and Powassan virus were examined using biophysical and computational...
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