Membrane protein biogenesis at the ER: the highways and byways

The Sec61 complex is the major protein translocation channel of the endoplasmic reticulum (ER), where it plays a central role in the biogenesis of membrane and secretory proteins. Whilst Sec61‐mediated protein translocation is typically coupled to polypeptide synthesis, suggestive of significant complexity, an obvious characteristic of this core translocation machinery is its surprising simplicity. Over thirty years after its initial discovery, we now understand that the Sec61 complex is in fact the central piece of an elaborate jigsaw puzzle, which can be partly solved using new research findings. We propose that the Sec61 complex acts as a dynamic hub for co‐translational protein translocation at the ER, proactively recruiting a range of accessory complexes that enhance and regulate its function in response to different protein clients. It is now clear that the Sec61 complex does not have a monopoly on co‐translational insertion, with some transmembrane proteins preferentially utilising the ER membrane complex instead. We also have a better understanding of post‐insertion events, where at least one membrane‐embedded chaperone complex can capture the newly inserted transmembrane domains of multi‐span proteins and co‐ordinate their assembly into a native structure. Having discovered this array of Sec61‐associated components and competitors, our next challenge is to understand how they act together in order to expand the range and complexity of the membrane proteins that can be synthesised at the ER. Furthermore, this diversity of components and pathways may open up new opportunities for targeted therapeutic interventions designed to selectively modulate protein biogenesis at the ER.

• Publication year

  2021

• Venue

  The FEBS Journal

• Publication date

  2021-05-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/febs.15905PMID 33960686
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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