Publikationsserver der Universitätsbibliothek Marburg

Titel: Untersuchung der Funktion der N-terminalen Verlängerung von GBP 130 von Plasmodium falciparum
Autor: Barniol, Luis F.
Weitere Beteiligte: Przyborski, Jude (PD Dr.)
Veröffentlicht: 2013
URN: urn:nbn:de:hebis:04-z2013-00802
DDC: Biowissenschaften, Biologie
Titel(trans.): Understading the ER-type n-terminal signalsequence of GBP 130 in plasmodium falciparum
Publikationsdatum: 2013-03-12


Proteintransport, signalsequence, Signalsequenz, Plasmodium falciparum, Plasmodium falciparum

Plasmodium falciparum exportiert Proteine in den Wirtserythrozyt, die die Wirtszelle morphologisch modifizieren. Eine wichtige Konsequenz dieser morphologischen Veränderung der Wirtszelle ist die Eigenschaft der infizierten Zellen an Rezeptoren im Endothel der Blutgefässe zu binden. Diese adhäsiven Eigenschaften sind verantwortlich für die klinischen Symptome der Malaria Krankheit. Die exportierten Proteine müssen den sekretorischen Weg des Parasiten und die den Parasiten umschließende Parasitophore Vakuole durchqueren, bevor sie das Zytosol oder die Plasmamembran der Wirtszelle erreichen. Der Fokus dieser Arbeit liegt auf dem Eintritt von Proteinen in den sekretorischen Weg des Parasiten, dabei insbesondere auf der Erkennung untypisch verlängerter Signalsequenzen. In dieser Arbeit wurde die Funktion der untypischen Signalsequenz des Glykophorin bindenden Proteins 130 (GBP 130) untersucht. Diese Signalsequenz besitzt eine ungewöhnliche Nterminale Verlängerung von 47 Aminosäuren (AS). Der Effekt dieser N-terminalen Verlängerung von GBP 130 auf die Proteinsortierung in Plasmodium wurde im Detail untersucht. Dabei konnte gezeigt werden, dass die N-terminale Verlängerung keinerlei Einfluss auf die Endbestimmung des Proteins hat und dass die Nterminale Verlängerung kompatibel mit dem Transport löslicher Proteine ist. Zudem wurde gezeigt, dass die verlängerte Signalsequenz von GBP 130 kein für Plasmodium spezifisches ER-Erkennungssignal ist, da sie auch vom sekretorischen Weg von Humanzellen erkannt wird.

The initial stages of the P. falciparum secretory pathway appear to be similar to that in higher eukaryotes, but with some important differences. It has been noted that, although many P. falciparum proteins contain so-called “canonical” signal peptides (with a central hydrophobic region, a hydrophilic N-region and a C-terminal region), a number of secreted proteins contain an unusual N-terminal region prior to the hydrophobic signal peptide (recessed signal peptides). These N-terminal sequences appear to target proteins to the ER, but how exactly this occurs, and the function of the extension remains unknown. For reasons that are currently not well understood, recessed signal sequences are found mostly attached to proteins predicted to be transported to the cytosol of the host erythrocyte. These proteins underlie the pathology of malaria infection, as they confer novel properties to the infected host cell. In this PhD thesis, we aim to dissect such unusual secretory signal peptides, with a view to understanding their function. We shall use several P. falciparum N-terminal regions to this end, including classical signal peptides, as well as proteins containing recessed hydrophobic domains.

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