Conserved motifs on the cytoplasmic face of the protein translocation channel are critical for the transition between resting and active conformations.

The Sec61 complex is the primary cotranslational protein translocation channel in yeast (). The structural transition between the closed inactive conformation of the Sec61 complex and its open and active conformation is thought to be promoted by binding of the ribosome nascent-chain complex to the cytoplasmic surface of the Sec61 complex. Here, we have analyzed new yeast Sec61 mutants that selectively interfere with cotranslational translocation across the endoplasmic reticulum.