The initial events in the localization of cell surface proteins include targeting of precursor molecules to the membrane and subsequent translocation across the membrane. The translocation reaction is mediated through a series of molecular interactions involving a number of protein factors. The trimeric SecY/Sec61 core complex, which is conserved throughout evolution, provides a proteinaceous pathway for translocation. The driving force for translocation is provided by the dynamic motion of the SecA ATPase in prokaryotes and by polypeptide elongation through the ribosome-Sec61 junction in eukaryotes.