7NFX

Mammalian ribosome nascent chain complex with SRP and SRP receptor in early state A

This is a non-PDB format compatible entry.

Summary for 7NFX

• Entry DOI: 10.2210/pdb7nfx/pdb
• EMDB information: 12303
• Descriptor: SRP RNA 7SL, uL30, 60S ribosomal protein L7a, ... (59 entities in total)
• Functional Keywords: signal recognition particle, protein targeting to the er membrane, ribosome
• Biological source: Homo sapiens; More
• Total number of polymer chains: 55
• Total formula weight: 2468070.52

Authors

Jomaa, A.,Lee, J.H.,Shan, S.,Ban, N. (deposition date: 2021-02-08, release date: 2021-06-02, Last modification date: 2024-05-01)

Primary citation

Lee, J.H.,Jomaa, A.,Chung, S.,Hwang Fu, Y.H.,Qian, R.,Sun, X.,Hsieh, H.H.,Chandrasekar, S.,Bi, X.,Mattei, S.,Boehringer, D.,Weiss, S.,Ban, N.,Shan, S.O.
Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER.
Sci Adv, 7:-, 2021

PubMed Abstract: The conserved signal recognition particle (SRP) cotranslationally delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum (ER). The molecular mechanism by which eukaryotic SRP transitions from cargo recognition in the cytosol to protein translocation at the ER is not understood. Here, structural, biochemical, and single-molecule studies show that this transition requires multiple sequential conformational rearrangements in the targeting complex initiated by guanosine triphosphatase (GTPase)-driven compaction of the SRP receptor (SR). Disruption of these rearrangements, particularly in mutant SRP54 linked to severe congenital neutropenia, uncouples the SRP/SR GTPase cycle from protein translocation. Structures of targeting intermediates reveal the molecular basis of early SRP-SR recognition and emphasize the role of eukaryote-specific elements in regulating targeting. Our results provide a molecular model for the structural and functional transitions of SRP throughout the targeting cycle and show that these transitions provide important points for biological regulation that can be perturbed in genetic diseases.

PubMed: 34020957
DOI: 10.1126/sciadv.abg0942

Experimental method

ELECTRON MICROSCOPY (3.2 Å)