Cotranslational protein translocation 2026-10-18
Cotranslational protein translocation is passage of a growing polypeptide chain across a membrane during biological translation. SRP recognizes an exposed hydrophobic ER signal sequence. The SRP receptor enables handoff to the Sec61 complex. Biological translation can slow during delivery; the ribosome remains on the cytosol side.[ref]
Membrane Protein Insertion at the Endoplasmic Reticulum by Sichen Shao and Ramanujan S. Hegde. Shao and Hegde, Membrane Protein Insertion at the Endoplasmic Reticulum, 2011; “Cotranslational Targeting”, Figure 3
The useful engineering feature is coordination: a targeting instruction can become accessible while the rest of its cargo is still being made. Recognition, docking and crossing remain distinct operations. A defect in any one can prevent successful import even when the protein primary structure contains an appropriate signal.
This route is not universal. Many tail-anchored proteins use delivery after biological translation, and their membrane-spanning segment lies near the C-terminus. Thus protein targeting signals need not be at the N-terminus.[ref]
Membrane Protein Insertion at the Endoplasmic Reticulum by Sichen Shao and Ramanujan S. Hegde. Shao and Hegde, 2011; “Posttranslational Membrane Protein Topogenesis”, Figure 6
Sec61 complex 2026-10-18
The Sec61 complex supports passage across the endoplasmic reticulum membrane and lateral entry of membrane-spanning segments into its lipid bilayer.[ref]
Membrane Protein Insertion at the Endoplasmic Reticulum by Sichen Shao and Ramanujan S. Hegde. Shao and Hegde, 2011; “The Sec61 Translocon”, Figure 4
Signal anchor 2026-10-18
A signal anchor combines targeting or initiation of membrane passage with a retained membrane-spanning segment. Its orientation determines which flanking part enters the ER lumen; a single internal signal can yield either orientation.[ref]
Membrane Protein Insertion at the Endoplasmic Reticulum by Sichen Shao and Ramanujan S. Hegde. Shao and Hegde, 2011; “Cotranslational Membrane Protein Topogenesis”, Figure 5
In the figure's stipulated internal-anchor example, the N-terminus remains in the cytosol and the C-terminus enters the ER lumen. Reversing that orientation would reverse which end is protected from an externally added protease. Merely counting one membrane-spanning segment cannot choose between the two.
Signal recognition particle 2026-10-18
The signal recognition particle is an RNA–protein targeting complex linking a ribosome-associated nascent chain to the SRP receptor.[ref]
Membrane Protein Insertion at the Endoplasmic Reticulum by Sichen Shao and Ramanujan S. Hegde. Shao and Hegde, 2011; “Cotranslational Targeting”, Figure 3
Signal recognition particle receptor 2026-10-18
The SRP receptor receives the SRP–ribosome–nascent chain complex for handoff to the translocon.[ref]
Membrane Protein Insertion at the Endoplasmic Reticulum by Sichen Shao and Ramanujan S. Hegde. Shao and Hegde, 2011; “Cotranslational Targeting”, Figure 3
Translocon 2026-10-18
A translocon is membrane machinery through which a polypeptide chain crosses or enters a membrane. In endoplasmic reticulum protein targeting, the Sec61 complex supplies the central channel.[ref]
Membrane Protein Insertion at the Endoplasmic Reticulum by Sichen Shao and Ramanujan S. Hegde. Shao and Hegde, 2011; “The Sec61 Translocon”, Figure 4