Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 TAT peptide across lipid membranes

摘要: The recombinant HIV-1 Tat protein contains a small region corresponding to residues 47YGRKKRRQRR57R, which is capable of translocating cargoes different molecular sizes, such as proteins, DNA, RNA, or drugs, across the cell membrane in an apparently energy-independent manner. pathway that these peptides follow for entry into has been subject strong controversy last decade. This peptide highly basic and hydrophilic. Therefore, central question any candidate mechanism answer how this hydrophilic able cross hydrophobic barrier imposed by membrane. We propose spontaneous translocation lipid involves interactions between phosphate groups on both sides bilayer, insertion charged side chains nucleate formation transient pore, followed diffusing pore surface. explains key ingredients, cooperativity among peptides, large positive charge, specifically arginine amino acids, contribute uptake. proposed also illustrates importance fluctuations. Indeed, mechanisms involve fluctuations structure, pores acid chains, may be common perhaps functions many functions.