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| Title | Structural analysis of the dynamic ribosome-translocon complex. |
|---|---|
| Journal, issue, pages | Elife, Vol. 13, Year 2024 |
| Publish date | Jun 18, 2024 |
 Authors | Aaron J O Lewis / Frank Zhong / Robert J Keenan / Ramanujan S Hegde /   |
| PubMed Abstract | The protein translocon at the endoplasmic reticulum comprises the Sec61 translocation channel and numerous accessory factors that collectively facilitate the biogenesis of secretory and membrane ...The protein translocon at the endoplasmic reticulum comprises the Sec61 translocation channel and numerous accessory factors that collectively facilitate the biogenesis of secretory and membrane proteins. Here, we leveraged recent advances in cryo-electron microscopy (cryo-EM) and structure prediction to derive insights into several novel configurations of the ribosome-translocon complex. We show how a transmembrane domain (TMD) in a looped configuration passes through the Sec61 lateral gate during membrane insertion; how a nascent chain can bind and constrain the conformation of ribosomal protein uL22; and how the translocon-associated protein (TRAP) complex can adjust its position during different stages of protein biogenesis. Most unexpectedly, we find that a large proportion of translocon complexes contains RAMP4 intercalated into Sec61's lateral gate, widening Sec61's central pore and contributing to its hydrophilic interior. These structures lead to mechanistic hypotheses for translocon function and highlight a remarkably plastic machinery whose conformations and composition adjust dynamically to its diverse range of substrates. |
 External links | Elife / PubMed:38896445 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.67961 - 2.90061 Å |
| Structure data | EMDB-19195, PDB-8rjb:  EMDB-19196: Structure of the rabbit 80S ribosome stalled on a 2-TMD rhodopsin intermediate in complex with Sec61, all-particle reconstruction EMDB-19197, PDB-8rjc: EMDB-19198, PDB-8rjd:  EMDB-19199: Structure of the rabbit 80S ribosome stalled on a 2-TMD rhodopsin intermediate in complex with Sec61, bound TRAP-alpha TMD  EMDB-19200: Structure of the rabbit 80S ribosome stalled on a 2-TMD rhodopsin intermediate in complex with Sec61-TRAP, conformation 1  EMDB-19201: Structure of the rabbit 80S ribosome stalled on a 2-TMD rhodopsin intermediate in complex with Sec61-TRAP, conformation 2  EMDB-19202: Structure of the rabbit 80S ribosome stalled on a 2-TMD rhodopsin intermediate in complex with Sec61, closed conformation 1  EMDB-19203: Structure of the rabbit 80S ribosome stalled on a 2-TMD rhodopsin intermediate in complex with Sec61, closed conformation 2  EMDB-19204: Structure of the rabbit 80S ribosome stalled on a 2-TMD rhodopsin intermediate in complex with Rho-bound Sec61 |
| Chemicals |  ChemComp-MG:  ChemComp-ZN: |
| Source |
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 Keywords | RIBOSOME / Membrane protein / Translocon / Transport |
canis lupus familiaris (dog)
oryctolagus cuniculus (rabbit)
bos taurus (cattle)
sus scrofa (pig)