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TitleMechanism of signal sequence handover from NAC to SRP on ribosomes during ER-protein targeting.
Journal, issue, pagesScience, Vol. 375, Issue 6583, Page 839-844, Year 2022
Publish dateFeb 25, 2022
AuthorsAhmad Jomaa / Martin Gamerdinger / Hao-Hsuan Hsieh / Annalena Wallisch / Viswanathan Chandrasekaran / Zeynel Ulusoy / Alain Scaiola / Ramanujan S Hegde / Shu-Ou Shan / Nenad Ban / Elke Deuerling /
PubMed AbstractThe nascent polypeptide-associated complex (NAC) interacts with newly synthesized proteins at the ribosomal tunnel exit and competes with the signal recognition particle (SRP) to prevent mistargeting ...The nascent polypeptide-associated complex (NAC) interacts with newly synthesized proteins at the ribosomal tunnel exit and competes with the signal recognition particle (SRP) to prevent mistargeting of cytosolic and mitochondrial polypeptides to the endoplasmic reticulum (ER). How NAC antagonizes SRP and how this is overcome by ER targeting signals are unknown. Here, we found that NAC uses two domains with opposing effects to control SRP access. The core globular domain prevented SRP from binding to signal-less ribosomes, whereas a flexibly attached domain transiently captured SRP to permit scanning of nascent chains. The emergence of an ER-targeting signal destabilized NAC's globular domain and facilitated SRP access to the nascent chain. These findings elucidate how NAC hands over the signal sequence to SRP and imparts specificity of protein localization.
External linksScience / PubMed:35201867 / PubMed Central
MethodsEM (single particle)
Resolution2.83 - 3.4 Å
Structure data

14191

7qwq

EMDB-14191, PDB-7qwq:
Ternary complex of ribosome nascent chain with SRP and NAC
Method: EM (single particle) / Resolution: 2.83 Å

14192

7qwr

EMDB-14192, PDB-7qwr:
Structure of the ribosome-nascent chain containing an ER signal sequence in complex with NAC
Method: EM (single particle) / Resolution: 2.9 Å

14193

7qws

EMDB-14193, PDB-7qws:
Structure of ribosome translating beta-tubulin in complex with TTC5 and NAC
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • oryctolagus cuniculus (rabbit)
  • homo sapiens (human)
KeywordsRIBOSOME / SRP / NAC / nascent chain / co-translational / Endoplasmic reticulum / co-translational protein targeting / co-translational folding

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