Translocation of Secretory Proteins Across the ER Membrane
■ Synthesis of secreted proteins; enzymes destined for the ER, Golgi complex, or lysosome; and integral plasmamembrane proteins begins on cytosolic ribosomes, which become attached to the membrane of the ER, forming the rough ER (see Figure 16-1, left).
■ The ER signal sequence on a nascent secretory protein consists of a segment of hydrophobic amino acids, generally located at the N-terminus.
■ In cotranslational translocation, the signal-recognition particle (SRP) first recognizes and binds the ER signal sequence on a nascent secretory protein and in turn is bound by an SRP receptor on the ER membrane, thereby targeting the ribosome/nascent chain complex to the ER.
■ The SRP and SRP receptor then mediate insertion of the nascent secretory protein into the translocon. Hydrolysis of GTP by the SRP and its receptor drive this docking process (see Figure 16-6). 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.
■ 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 chap-erone BiP, which stabilizes the entering polypeptide (see Figure 16-9).
■ 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.
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