Thesis
THE INTERACTION OF THE VARIANT SURFACE GLYCOPROTEIN OF TRYPANOSOMA BRUCEI WITH LIPID MONOLAYERS
Autor
Infante Rivas, Ramon Benito
Institución
Resumen
ABSTRACT
The bloodstream form of Trypanosoma brucei is completely covered
By a thick surface coat which is composed of molecules of variant-s specific surface glycoproteins (VSGs). An understanding of the mode attachment of VSG to the plasma membrane is important in the search for new treatments against this parasite.
The use of lipid monolayers with measurement of surface pressure, surface potential and surface radioactivity show that there is a weak interaction between water-soluble VSG and phosphatidyl choline or phosphatidyl ethanolamine and no interaction with sphingomyelin.
The interaction of VSG with sterols, however, is significantly stronger than for phospholipids as estimated by changes in surface pressure using either force-area curves or film penetration experiments.
the order of the VSG-lipid interaction is as follows:
cholesterol > ergosterol > phospholipids > sphingomyelin.
The preferential interaction of VSG with sterols appears to show a certain degree of chemical structure recognition as deduced from studies using cholesterol derivatives and competition with filipin for cholesterol. Thus, substitution of the 3β-OH group of cholesterol by either negatively charged groups or neutral groups inhibit the film penetration, whilst positively charged substituents maintain or enhance the film penetration.
Dissociation of VSG with sodium cholate results in a strong interaction of VSG with phosphatídyl choline and spingomyelin: this does not happen with cholesterol. This suggests that dissociation of VSG into monomers is a necessary pre-requisite for film penetration.
Studies of the VSG-lipid interaction using liposomes support the finding of a weak interaction of VSG with phospholipids as determined with the monolayer technique. It is suggested that net positive charges, or intrinsic proteins, or both, are necessary on the parasite surface stabilize the binding of VSG to the plasma membrane. La tesis fue escaneada debido que en su fecha de presentación no existían los archivos electrónicos. Debido al tamaño en Mb, se dividio en 3 ficheros CDCH - UCV, Darwin College, Cambridge.