Key Concepts of Section 13.1

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Key Concepts of Section 13.1

Targeting Proteins To and Across the ER Membrane

  • Synthesis of secreted proteins, integral plasma-membrane proteins, and proteins destined for the ER, Golgi complex, or lysosome begins on cytosolic ribosomes, which become attached to the membrane of the ER, forming the rough ER (see Figure 13-1, left).

  • The ER signal sequence on a nascent secretory protein is located at the N-terminus and contains a sequence of hydrophobic amino acids.

  • In cotranslational translocation, the signal recognition particle (SRP) first recognizes and binds the ER signal sequence on a nascent secretory protein, then is bound in turn by an SRP receptor on the ER membrane, thereby targeting the nascent polypeptide chain–ribosome complex to the ER.

  • The SRP and SRP receptor then mediate insertion of the nascent secretory protein into the translocon (Sec61 complex). Hydrolysis of two molecules of GTP by the SRP and its receptor cause the dissociation of SRP (see Figures 13-5 and 13-6). As the ribosome attached to the translocon continues translation, the unfolded protein chain is extruded into the ER lumen. No additional energy is required for translocation.

  • The translocon contains a central channel lined with hydrophobic residues that allows transit of an unfolded protein chain while remaining sealed to ions and small hydrophilic molecules. In addition, the channel is gated so that it is open only when a polypeptide is being translocated.

  • In post-translational translocation, a completed secretory protein is targeted to the ER membrane by interaction of the signal sequence with the translocon. The polypeptide chain is then pulled into the ER by a ratcheting mechanism that requires ATP hydrolysis by the chaperone BiP, which stabilizes the entering polypeptide (see Figure 13-9). In bacteria, the driving force for post-translational translocation comes from SecA, a cytosolic ATPase that pushes polypeptides through the translocon channel.

  • In both cotranslational and post-translational translocation, a signal peptidase in the ER membrane cleaves the ER signal sequence from a secretory protein soon after the N-terminus enters the lumen.