BIOGENESIS OF POLYTOPIC MEMBRANE-PROTEINS - MEMBRANE SEGMENTS OF P-GLYCOPROTEIN SEQUENTIALLY TRANSLOCATE TO SPAN THE ER MEMBRANE

The initial steps in the biogenesis of membrane proteins parallel thos e of secretory proteins. However, membrane proteins contain a signal t o stop translocation across the membrane. For polytopic membrane prote ins, those with multiple transmembrane segments, little is known of th e temporal sequence or relationship between synthesis of the nascent p roteins, translocation, folding, and integration of the membrane segme nts into the bilayer. Here we demonstrate that latent membrane segment s translocate sequentially as they emerge from the ribosome and do not accumulate on the cytosolic side to form loops, or larger structures, prior to translocation across the membrane.