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Editorial
. 2024 May 24:13:e98548.
doi: 10.7554/eLife.98548.

RAMPing up knowledge of the translocon

Dimitrios Vismpas  1 , Friedrich Förster  1
Affiliations
Editorial

RAMPing up knowledge of the translocon

Dimitrios Vismpas et al. Elife. .

Abstract

Advanced cryo-EM approaches reveal surprising insights into the molecular structure that allows nascent proteins to be inserted into the membrane of the endoplasmic reticulum.

Keywords: RAMP4; Sec61; cell biology; cryo-EM; molecular biophysics; multipass translocon; none; ribosomes; structural biology.

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Conflict of interest statement

DV, FF No competing interests declared

Figures

Figure 1.
Figure 1.. Molecular structures of the different intermediates of ribosome-bound multipass translocons forming during the biogenesis of Rhoext.
Lewis et al. examined the structure of various intermediates of the multipass translocon as it processed a nascent Rhoext construct emerging from ribosomes (small and large subunits in light and dark grey, respectively, with ribosomal protein uL22 in hot pink). This highly dynamic complex is formed of a Sec61 channel (light and dark blue) studded through the membrane of the endoplasmic reticulum, which can associate with various molecular actors. (A) In a fully loaded multipass translocon, Sec61 binds to the chaperone PAT, which connects to the ribosomal protein uL22 via its CCD47 subunit (aqua). In this conformation, the lateral gate (a sideway exit that allows the insertion of transmembrane domains into the membrane) is closed. (B) Top: In one type of PAT-less multipass translocon, the second transmembrane domain in the Rhoext construct (RhoTM2; green) is bound to the lateral gate of Sec61, which is open. Bottom: Certain transmembrane segments of RAMP4 (orange) can get temporarily replaced by the hydrophobic domains of the protein processed by the translocon, such as RhoTM2 (green; here bound to Sec61). In addition, in the absence of CCDC47 the uL22 C-terminal helix (red) of the ribosome gets ordered and forms a lid blocking an escape route for nascent proteins to the cytosol. (C) In the other type of open PAT-less multipass translocon (in which the lateral gate is also open), RAMP4 (orange) binds to Sec61 and acts as a fourth subunit for the channel, potentially participating in its opening.
See this image and copyright information in PMC

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  • doi: 10.7554/eLife.95814

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References

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