7QWR

Structure of the ribosome-nascent chain containing an ER signal sequence in complex with NAC

This is a non-PDB format compatible entry.

Summary for 7QWR

• Entry DOI: 10.2210/pdb7qwr/pdb
• EMDB information: 14192
• Descriptor: Nascent chain pre-prolactin, Ribosomal_L18_c domain-containing protein, Ribosomal protein L32, ... (50 entities in total)
• Functional Keywords: ribosome, srp, nac, nascent chain, co-translational, endoplasmic reticulum, co-translational protein targeting, co-translational folding
• Biological source: Homo sapiens; More
• Total number of polymer chains: 48
• Total formula weight: 2543549.63

Authors

Jomaa, A.,Gamerdinger, M.,Hsieh, H.,Wallisch, A.,Chandrasekaran, V.,Ulusoy, Z.,Scaiola, A.,Hegde, R.,Shan, S.,Ban, N.,Deuerling, E. (deposition date: 2022-01-25, release date: 2022-03-09, Last modification date: 2024-07-17)

Primary citation

Jomaa, A.,Gamerdinger, M.,Hsieh, H.H.,Wallisch, A.,Chandrasekaran, V.,Ulusoy, Z.,Scaiola, A.,Hegde, R.S.,Shan, S.O.,Ban, N.,Deuerling, E.
Mechanism of signal sequence handover from NAC to SRP on ribosomes during ER-protein targeting.
Science, 375:839-844, 2022

PubMed Abstract: 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.

PubMed: 35201867
DOI: 10.1126/science.abl6459

Experimental method

ELECTRON MICROSCOPY (2.9 Å)