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Protein targeting Created 2026-10-13 Updated 2026-10-18
Protein targeting directs a protein to its cellular destination. Synthesis in the cytosol does not imply that the protein works there.
For entry into the endoplasmic reticulum, distinguish three questions: does the nascent chain reach the membrane, does part of it cross into the ER lumen, and does a segment remain embedded as a transmembrane protein? Cotranslational protein translocation couples these events to biological translation. A signal peptide can initiate delivery without specifying the eventual destination of the mature protein.
Protein targeting to the endoplasmic reticulum: delivery and three possible outcomes
. Original pathway and membrane topology schematic. The upper row separates SRP recognition, membrane docking and passage through a translocon. Lower cartoons stipulate a soluble cargo, a cleaved signal peptide plus retained stop-transfer sequence, and an uncleaved internal signal anchor. Each drawn terminus is labeled; the internal-anchor orientation is one possibility. Shapes and lengths are illustrative, with no molecular coordinates or measured timings. Details.
This distinction matters experimentally. Finding a protein in a membrane-containing centrifugation pellet could reflect surface binding or protein aggregation. The microsomal protein import experiment instead asks whether an intact membrane prevents an external protease from reaching the product. That tests accessibility across a barrier, rather than proximity to it.
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