Cytosolic protein translocation factors. Is SRP still unique?

The control of protein traffic into eukaryotic membrane bounded organelles or across the prokaryotic plasma membrane is dependent upon each new molecule being directed to the appropriate translocation pathway. The requirement for discrete signal sequences in targeting proteins to the correct membrane has been well documented. There is now growing evidence, however, that after preproteins are released from ribosomes, they must be in a non-rigid conformation in order to be translocated across membranes (reviewed in Meyer, 1988, and Randall and Hardy, 1989). Several cytosolic proteins in different systems have been proposed to preserve such a translocation-competent conformation. These molecules may bind to loosely folded proteins (including, but not necessarily restricted to, preproteins) at a variety of sites via hydrophobic or other interactions. In this way, they may slow the folding of the bound proteins into conformations that are unsuitable for interaction with specific signal recognition and translocation proteins. These factors have been postulated to be components of a preprotein recognition and targeting apparatus, but with the exception of the signal recognition particle (SRP), no direct interaction with preprotein signal sequences or specific membrane receptors as part of the translocation reaction has been demonstrated convincingly. In addition to fulfilling these criteria for an essential component of the translocation machinery, SRP may also be unique because it appears to function exclusively during preprotein synthesis. Hence, it may bypass altogether the problem of preproteins adopting unsuitable conformations before crossing the membrane.