Peptides direct across the cellular membrane
Several types of peptides, including penetratin, MPG, CADY, pVec and a variety of CPPs, can translocate directly across the plasma membrane. This is achieved via a helical conformational change which promotes the peptide’s insertion into the membrane by creating transient pores.
Some arginine-rich peptides, such as TAT (translocator of AMPs), are able to cross the membrane through an additional mechanism. When a TAT concentration threshold is reached, phosphate groups from neighboring phospholipids are drawn to the peptide. This process is similar to the way in which VEGF and its receptor, VEGFR, induce macropinocytosis of the cell surface.
In Streptococci, YSIRK/GS motif signal peptides are found in surface proteins that either arrive at ring-like distribution centers or assembly sites inside the cell wall envelope (clumping factor A, fibronectin binding protein B, serine-aspartate repeat proteins A and D, SasA, SdrC and SdrD) or on the cell pole (surface protein A, ClfA). Other Gram-positive bacteria like Listeria monocytogenes and Staphylococcus aureus have YSIRK/GS motif signal molecules distributed as discrete assembly sites.
These findings have prompted researchers to develop methods for peptides to be engineered to cross the cellular membrane. These methods often involve tagging a peptide with a radioactive functional group, which can be used to determine the distribution and pharmacokinetics of a designed peptide or to study its effects on biological function.