Die biochemische Analyse des Plasmodium falciparum Zytoadhärenz Moleküls PfEmp1 zeigt einen potentiell neuen Mechanismus für die Insertion von Oberflächenproteinen in Membranen
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Philipps-Universität Marburg
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Abstract
The Plasmodium falciparum cytoadherence factor
PfEmp1 is expressed on the surface of red blood cells where it
interacts with various endothelial receptors leading to the
sequestration of infected red blood cells in blood capillaries.
In addition, PfEmp1 undergoes antigenic variation giving rise
to the generation of irrelevant antibodies in the immune
response. Thus PfEmp1 is a major factor which contributes to
the severe pathology of malaria. PfEmp1 possesses a hydrophobic
segment in the vicinity of the carboxy end which according to a
commonly accepted view constitutes a transmembrane helix
anchoring the protein into the erythrocyte membrane. This model
provides a protein secretion machinery in red blood cells,
which by themselves are incapable of the synthesis and
trafficking of proteins. In this thesis the transport model on
PfEmp1 was issued by a precise biochemical examination
resulting in to the general view on PfEmp1 trafficking
conflicting data that suggest a novel model on synthesis and
transport of the protein. After treatment of infected cells
with the protein secretion blocking agent brefeldin A PfEmp1
was retained in the parasite. In contrast to integral membrane
proteins the protein could be extracted with alkaline carbonate
buffer, typical of peripheral membrane proteins. Another goal
of this thesis was the development of an assay that allows to
investigate transport vesicles such as suggested to be involved
in the secretion of PfEmp1. No association of the protein with
vesicles was found. Once the protein had been secreted into the
host cell it could be extracted under conditions that left
integral membrane proteins insoluble. PfEmp1 of the red cell
membrane could be extracted with urea which integral membrane
proteins of the red cell membrane resisted. Further, PfEmp1
could be separated from these marker membrane proteins by
density gradient centrifugation after urea treatment. The
results of this thesis imply a novel picture of the membrane
association of PfEmp1. The protein presumably becomes secreted
as a peripheral membrane protein or as part of a protein
complex. By an unknown mechanism on the basis of protein
interaction the protein is targeted to the red cell surface
where it is inserted into the membrane keeping the hydrophobic
segment of the protein bound to proteins.
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Dates
Created: 2004Issued: 2004-03-18Updated: 2011-08-10
Faculty
Fachbereich Biologie
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Adesion Membrane ProteineProtein TransportCellular AdhesionPlasmodium falciparumMalaria tropica
DFG-subjects
Plasmodium falciparum , MembranproteineZelladhäsionMalaria tropicaAdhäsion , Proteintransport
DDC-Numbers
570
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Papakrivos, Janni (128940247): Die biochemische Analyse des Plasmodium falciparum Zytoadhärenz Moleküls PfEmp1 zeigt einen potentiell neuen Mechanismus für die Insertion von Oberflächenproteinen in Membranen. : Philipps-Universität Marburg 2004-03-18. DOI: https://doi.org/10.17192/z2004.0096.
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This item has been published with the following license: In Copyright