Lipid modification of proteins and their membrane transport.

Abstract

An effective method for artificial attachment of lipid anchors to water-soluble proteins has been developed. To this end, a protein molecule is modified in a system of reversed micelles by a water-insoluble reagent, e.g. fatty acid chloride. Fatty acylated proteins acquire an ability to translocate across lipid membranes and penetrate intact cells. This principle of imparting transmembrane properties to water-soluble proteins makes it possible to realize in vivo a direct transport of antibodies across the hemato-encephalic barrier into the brain and to develop a method for virus suppression by fatty acylated anti-viral antibodies capable of penetrating infected cells. The effect of a drastic increase in the biological activity of exogenous protein factors, e.g. Staphylococcus aureus enterotoxin A, as a result of their artificial fatty acylation has been discovered. The above-mentioned phenomena are discussed in relation to the in vivo data, indicating that post-translational modification of proteins by fatty acids and phospholipids is very widespread in nature and evidently plays an important role in protein transport and sorting. In this connection, lipid modification of proteins is regarded as a possible general step of protein transport in vivo.