Transmembrane segments of nascent polytopic membrane proteins control cytosol/ER targeting during membrane integration

Vastly different folded transmembrane segments of nascent multispanning membrane proteins each induce structural changes in the ribosome tunnel and translocon that target the loops of the growing polypeptide alternately into the cytosol or ER lumen

Polytopic membrane protein folding at L17 in the ribosome tunnel initiates cyclical changes at the translocon

Interaction between L17 in the ribosome tunnel and folded nascent chain transmembrane segments during multi-spanning membrane protein synthesis triggers structural rearrangements in the ribosome that cause switching between cytosolic and ER lumenal targeting of the growing polypeptide