Targets membrane

Melikyan GB, Egelhofer M, von Laer D (2006) Membrane-anchored inhibitory peptides capture human immunodeficiency virus type 1 gp41 conformations that engage the target membrane prior to fusion, J Virol 80 3249-3258... 

Based largely on a proposal by Rothman and colleagues, anterograde vesicular transport can be considered to occur in eight steps (Figure 46-7). The basic concept is that each transport vesicle bears a unique address marker consisting of one or more v-SNARE proteins, while each target membrane bears one or more complementary t-SNARE proteins with which the former interact specifically. 

Step 5 Vesicle targeting is achieved via members of a family of integral proteins, termed v-SNAREs, that tag the vesicle during its budding. v-SNAREs pair with cognate t-SNAREs in the target membrane to dock the vesicle. 

Most transport vesicles bud off as coated vesicles, with a unique set of proteins decorating their cytosolic surface 141 GTP-binding proteins, such as the small monomeric GTPases and heterotrimeric GTPases (G proteins) facilitate membrane transport 142 SNARE proteins and Rabs control recognition of specific target membranes 143... 

Unloading of the transport vesicle cargo to the target membrane occurs by membrane fusion 143... 

Sampo, B., Kaech, S., Kunz, S. and Banker, G. Two distinct mechanisms target membrane proteins to the axonal surface. Neuron 37 611-624, 2003. 

Further investigations with bimanyl-labeled K-Ras4B peptides demonstrated that relatively small differences in membrane charging (approximately 10 mol %) are sufficient for an electrostatic enrichment in the more negative environment [230]. With the farnesyl group as a hydrophobic anchor, the peptide is still mobile and can swap between vesicles but may find its target membrane with the sensitive surface potential-sensing function of its lysine residues. 

Eukaryotic cells utilize an efficient transport system that delivers macromolecules fast and secure to their destination. In the case of the small GTP binding proteins of the Ras family the modified C-terminus seems to be sufficient for addressing the polypeptide to its target membrane (in the case of Ras itself the plasma membrane). Lipopeptides with the C-terminal structure of N-Ras (either a pen-tamer with a C-terminal carboxymethylation and farnesylation or a heptapeptide with a palmitoyl thioester in addition) and a N-terminal 7-nitrobenz-2-oxa-l,3-diazolyl (NBD) fluorophore were microin-jected into NIH3T3 fibroblast cells and the distribution of the fluorophore was monitored by confocal laser fluorescence microscopy. Enrichment of the protein in the plasma membrane was efficient only for peptides with two hydrophobic modification sites, while the farnesylated but not palmitoylated peptide was distributed in the cytosol.1121... 

It is obvious why the spectroscopist wants to investigate the structure of integral membrane proteins or enzymes, whose biological action is linked to the presence of phospholipids such as phospholipase, in a membrane-mimicking environment Why such an environment should also be used for other peptides like hormones becomes more clear when we take into account the membrane compartment theory [10-12] as postulated by R. Schwyzer. This theory states that peptides that target membrane-embedded receptors... 

In terms of targeting, membrane translocation domains lack specificity for particnlar cells or tissues. Therefore, these domains shonld be combined with targeting domains snch as those discussed in the previous section. In snch a constrnct, the targeting domain wiU ensnre a rapid accumulation at the surface of a specific cell type and the translocation domain will facilitate entry into the cytosol of the target cells. 

The kinetic control of vesicle transport, from vesicle budding in the Golgi (and other origins) to fusion of the vesicle with the target membrane, is currently a vigorous area of research. The formation of COP-coated vesicles... 

For target selection, adhesion molecules are expressed on the surface of endothelial cells. For this purpose, sialyl Lewis X is used as the guide molecule in the case of expression of P- and E-selectins for TNFa-activated HUVEC (human umbilical vein endothelial cells). Thus, targeting membrane-bound antigens in situ is also possible with this technique. 

After synthesis on the smooth ER, the polar lipids, including the glycerophospholipids, sphingolipids, and glycolipids, are inserted into specific cellular membranes in specific proportions, by mechanisms not yet understood. Membrane lipids are insoluble in water, so they cannot simply diffuse from their point of synthesis (the ER) to their point of insertion. Instead, they are delivered in membrane vesicles that bud from the Golgi complex then move to and fuse with the target membrane (see Fig. 11-23). Cytosolic proteins also bind phospholipids and sterols and transport them between cellular membranes. These mechanisms contribute to the establishment of the characteristic lipid compositions of organelle membranes (see Fig. 11-2). 

---