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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]

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]

Researcher in protein targeting and membrane biogenesis. With Sichen Shao, Hegde analyzed insertion of membrane proteins at the endoplasmic reticulum, connecting protein properties with the machinery that handles them.^[ref]

The Sec61 complex supports passage across the endoplasmic reticulum membrane and lateral entry of membrane-spanning segments into its lipid bilayer.^[ref]

Cell biologist studying insertion of membrane proteins at the endoplasmic reticulum. Shao and Ramanujan S. Hegde analyzed how cellular machinery delivers and inserts hydrophobic proteins into a membrane.^[ref]

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]

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.

The signal recognition particle is an RNA–protein targeting complex linking a ribosome-associated nascent chain to the SRP receptor.^[ref]

The SRP receptor receives the SRP–ribosome–nascent chain complex for handoff to the translocon.^[ref]

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]