Download or read book Characterization of the Protein Export Steps at the Parasite host Cell Interface of the Human Malaria Parasite Plasmodium Falciparum Welch 1897 written by Paolo Mesén-Ramírez and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of the Protein Export Steps at the Parasite host Cell Interface of the Human Malaria Parasite Plasmodium Falciparum Welch 1897 written by Paolo Mesén-Ramírez and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization and Visualization of Protein Export in the Human Malaria Parasite Plasmodium Falciparum Welch 1897 written by Christof Grüring and published by . This book was released on 2011 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Functional Analysis of Trophozoite and Schizont exported Proteins of the Human Malaria Parasite Plasmodium Falciparum Welch 1897 written by Jan Stäcker and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Analysis of Protein Translocation at the Interface Between the Malaria Parasite Plasmodium Falciparum and Its Host Cell written by Ferdinand Reinsch and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book An Alternative Secretory Pathway in the Malaria Parasite Plasmodium falciparum written by Thuvaraka Thavayogarajah and published by GRIN Verlag. This book was released on 2017-08-31 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt: Doctoral Thesis / Dissertation from the year 2014 in the subject Biology - Diseases, Health, Nutrition, grade: 1.3, University of Marburg (European virtual Institute for Malaria Research), language: English, abstract: This study focuses on the discovery of an alternative secretory pathway to the ER/Golgi route in the malaria parasite P. falciparum in infected RBCs. Two proteins appeared to be promising candidates of an alternative secretory pathway: the PfADP-ribosylation factor 1 (ARF1) and the Pfadenylate kinase 2 (AK2). Both proteins contained an N-myristoylation site at their N-terminus, which is indicative for N-myristoylation. N-myristoylation is a co-translational modification of a protein, whereby a fatty acid (myristate) is irreversibly attached to the glycine residue at the N-terminus of a protein via the PfN-myristoyltransferase (NMT). A preceding proteomic analysis of the parasitophorous vacuole and a reporter construct study proposed for both PfARF1 (determined by a proteomic study) and PfAK2 (determined by a reporter construct study) PV localization although both proteins lacked a signal peptide. That’s why it was hypothesized whether or not N-myristoylation would drive protein secretion across the parasite plasma membrane (PPM). The subcellular localization of the PfARF1/GFP parasites and the PfAK2/GFP parasites, respectively, were analyzed via epifluorescence microscopy and biochemical methods. In parallel, another batch of reporter constructs were generated and analyzed, where the N-myristoylation site of PfARF1 (this study) and PfAK2 (Ma et al., 2012), respectively, was removed (PfARF1G2A/GFP and PfAK2G2A/GFP). Live cell imaging showed that the fusion protein ARF1/GFP was localized as dot-like structures in the parasite. In contrast, the phenotype of the fusion protein of the PfARF1G2A/GFP parasites showed an evenly distributed signal in the parasite cytosol. Further analysis of the subcellular localization of the PfARF1 strongly supports its localization to compartments of the early secretory pathway of the parasite, but no localization in the PV. In contrast, the fusion protein PfAK2/GFP localized to a ring-like structure around the parasite indicating PV localization. The PfAK2G2A/GFP parasites showed a cytosolic localization of the fusion protein (Ma et al., 2012). Biochemical analyses revaled that the fusion protein PfAK2/GFP was secreted into the PV when the N-myristoylation site was present. Furthermore, it could be shown that the N-terminus of the PfAK2 protein is sufficient for parasite plasma membrane targeting, stable membrane anchoring and subsequent protein translocation across the PPM.
Download or read book Characterisation of the Plasmodium Falciparum Export Complex written by Brendan Elsworth and published by . This book was released on 2015 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium parasites extensively remodel the mammalian host cells they infect, namely the erythrocytes and hepatocytes. This is achieved through exporting hundreds of parasite proteins into the host where they play many virulence related roles including altering membrane permeability to acquire nutrients for rapid growth and for increasing immune evasion. Proteins are secreted from the parasite into the vacuole that surrounds them, where they must then pass across the parasitophorous vacuole membrane (PVM) to gain access to the host cytoplasm. It has previously been shown that a protein complex, the Plasmodium Translocon of EXported proteins (PTEX), is found on the PVM and is most likely the protein translocon responsible for this export process. To validate and further dissect PTEX function, a conditional expression system that utilizes the glmS riboswitch was employed to conditionally knockdown the levels of PTEX150 within parasites. Using this approach, even a relatively low level of PTEX150 knockdown lead to a significant decrease in the ability of the parasites to export proteins across the PVM. This failure of protein export across the PVM arrested growth and eventually caused parasite death. Interestingly, the export of all classes of protein cargoes tested, including PfEMP1, were blocked upon PTEX150 knockdown suggesting PTEX may serve as a single portal for export. This demonstrates the importance of PTEX to the malaria parasite and validates it as a potent drug target, since blocking it would prevent hundreds of exported proteins from reaching their functional destinations. To further investigate the specific function of PTEX150 we performed C-terminal truncations in order to generate a parasite line with a partially defective protein. These lines showed destabilisation of the PTEX complex, suggesting that the C-terminus of PTEX150, while not essential for PTEX function or the absolute binding of the other components, is required for stabilising the PTEX complex. Interestingly, these parasites did not show a defect in either their ability to grow or export proteins. To further investigate the effect of PTEX150 knockdown on parasite health the new permeability pathways (NPPs) were investigated. To do this a novel method was developed to investigate NPP function using luciferase. This method is highly sensitive, reducing the amount of parasites required as well as removing the need to purify parasites from culture. The effect of PTEX150 knockdown on NPPs was unclear using this method. Due to the high sensitivity and ease of this method it was developed as a HTS to discover NPP inhibitors. Using this method the malaria box of 400 compounds was screened. Importantly, two compounds, MMV020439and MMV007571, showed inhibitory activity significantly higher than the control compound NPPB.
Download or read book Visualization and Characterization of Endocytic Processes in the Human Malaria Parasite P Falciparum Welch 1897 written by Sven Flemming and published by . This book was released on 2015 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of the RIFIN Protein Family of the Malaria Parasite Plasmodium Falciparum Welch 1897 written by Michaela Petter and published by . This book was released on 2007 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of Adhesion Ligand Phosphorylation in the Malaria Parasite Plasmodium Falciparum Welch 1897 written by Klemens Engelberg and published by . This book was released on 2012 with total page 109 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification and Functional Analysis of Proteins Involved in Host Cell Cytosol Uptake of the Human Malaria Parasite Plasmodium Falciparum written by Ricarda Sabitzki and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification of Proteins Involved in Host Cell Cytosol Uptake in the Human Malaria Parasite Plasmodium Falciparum written by Ernst Georg Wolfgang Jonscher and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification and Characterization of Invasion related Proteins of the Malaria Parasite Plasmodium Falciparum Welch 1892 written by Louisa Wilcke and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Vesicle Targeting in Plasmodium Falciparum written by Lawrence Sumanjah Ayong and published by . This book was released on 2009 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins of the SNARE (Soluble N-ethylmaleimide sensitive factor attachment protein receptor) super-family have been characterized as playing an essential role in vesicle targeting and fusion in all eukaryotes. The intracellular malaria parasite Plasmodium falciparum exhibits an unusual endomembrane system that is characterized by an unstacked Golgi apparatus, a developmentally induced apical complex, and various organellar structures of parasite origin in the infected host cells. How malaria parasites target nuclear-encoded proteins to these novel compartments is a central question in Plasmodium cell biology. Ultrastructural studies elsewhere have implicated the participation of specialized vesicular elements in transport of virulence proteins, including various cytoadherance and host cell remodeling factors, into the infected erythrocyte cytoplasm. However, little is known about the machineries that define the directionality of vesicle trafficking in malaria parasites. We hypothesized that the P. falciparum SNARE proteins would exhibit novel features required for vesicle targeting to the parasite-specific compartments. We then identified for the first time and confirmed the expression of eighteen SNARE genes in P. falciparum. Members of the PfSNAREs exhibit atypical structural features (Ayong et al., 2007, Molecular & Biochemical Parasitology, 152(2), 113-122). Among the atypical PfSNAREs, PfSec22 contains an unusual insertion of the Plasmodium export element (PEXEL) within its profilin-like longin domain, preceded by an N-terminal hydrophobic segment.
Download or read book CryoEM Enabled Approaches to Structure Determination of Endogenous Protein Complexes Implicated in the Pathogenesis of the Malaria Parasite Plasmodium Falciparum written by Chi-Min Ho and published by . This book was released on 2019 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt: The complexity and breadth of the host-cell remodeling machinery in the malaria parasite P. falciparum make it a rich and exciting system for the study of host-pathogen interfaces, particularly as many of the molecular mechanisms underlying this parasite's ability to hijack human red blood cells remain unclear. Furthermore, the P. falciparum proteome has proven recalcitrant to structural and biochemical characterization using recombinant methods, making it an intriguing model system for the development of new methods that leverage recent advances in cryoEM to enable structural studies of previously intractable systems at near-atomic resolution. The work presented here makes significant contributions in both these regards. First, we use a targeted, CRISPR-enabled "top down" approach to determine near-atomic resolution structures of the unique malaria parasite translocon PTEX, which we purified directly from P. falciparum parasites in multiple functional states, yielding the first near-atomic resolution cryoEM structures of a protein isolated directly from an endogenous source using an epitope tag inserted into the endogenous locus with CRISPR-Cas9 gene editing. We then developed a "bottom up" endogenous structural proteomics method whereby protein complexes enriched directly from the cellular milieu are identified by imaging and structure determination using cryoEM and mass spectrometry. As a proof of principle, we successfully used this approach to obtain near-atomic resolution structures of multiple protein complexes from the P. falciparum proteome, which has previously proven recalcitrant to expression in recombinant systems, precluding structure determination by X-ray crystallography or NMR. The body of work described here addresses a known need for methods that overcome the limitations of structural biology approaches that depend on recombinant systems, opening the door for high resolution structure determination of a vast number of previously intractable biological systems.
Download or read book Global Screening and Characterization of Plasmodium Falciparum Welch 1897 Merozoite Putative Invasion related Proteins written by Ana Lidia Cabrera-Aguirre and published by . This book was released on 2010 with total page 30 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Gene Vaccines written by Josef Thalhamer and published by Springer Science & Business Media. This book was released on 2011-08-31 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: The induction of antigen-specific immune responses after in vivo transfection with expression plasmids has triggered a revolution of vaccine research. After a first hype, evoked by the fascinating options of this method, clinical studies did not reach the ambitious aims and a phase of disillusion ensued. It became obvious that Gene vaccines displayed a weaker immunogenicity in humans than had been observed in the mouse models. Meanwhile these hurdles have been overcome and gene vaccines undergo a renaissance. The present book gives an update of the “world of naked gene vaccines”, namely DNA and RNA vaccines. Its content ranges from general mechanisms, inherent immunostimulatory properties and the vast potential to modulate immune responses, to recent successful clinical studies and approved veterinary gene vaccines. Beyond the state-of-the-art of genetic immunization, the reader will be stimulated with a chapter addressing “burning questions”.
