8B6C

Cryo-EM structure of ribosome-Sec61 in complex with cyclotriazadisulfonamide derivative CK147

This is a non-PDB format compatible entry.

Summary for 8B6C

• Entry DOI: 10.2210/pdb8b6c/pdb
• Related: 8B5L
• EMDB information: 15863
• Descriptor: 60S ribosomal protein L21, 60S ribosomal protein L7a, 60S ribosomal protein L11, ... (50 entities in total)
• Functional Keywords: ribosome, sec61, trap, translocon, translation, rna binding protein, eef2, ck147, cada, translocon inhibitor, 80s, 60s, 40s, cyclotriazadisulfonamide, membrane protein
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 47
• Total formula weight: 2505605.89

Authors

Pauwels, E.,Shewakramani, N.R.,De Wijngaert, B.,Vermeire, K.,Das, K. (deposition date: 2022-09-26, release date: 2023-02-22, Last modification date: 2023-03-15)

Primary citation

Pauwels, E.,Shewakramani, N.R.,De Wijngaert, B.,Camps, A.,Provinciael, B.,Stroobants, J.,Kalies, K.U.,Hartmann, E.,Maes, P.,Vermeire, K.,Das, K.
Structural insights into TRAP association with ribosome-Sec61 complex and translocon inhibition by a CADA derivative.
Sci Adv, 9:eadf0797-eadf0797, 2023

PubMed Abstract: During cotranslational translocation, the signal peptide of a nascent chain binds Sec61 translocon to initiate protein transport through the endoplasmic reticulum (ER) membrane. Our cryo-electron microscopy structure of ribosome-Sec61 shows binding of an ordered heterotetrameric translocon-associated protein (TRAP) complex, in which TRAP-γ is anchored at two adjacent positions of 28 ribosomal RNA and interacts with ribosomal protein L38 and Sec61α/γ. Four transmembrane helices (TMHs) of TRAP-γ cluster with one C-terminal helix of each α, β, and δ subunits. The seven TMH bundle helps position a crescent-shaped trimeric TRAP-α/β/δ core in the ER lumen, facing the Sec61 channel. Further, our in vitro assay establishes the cyclotriazadisulfonamide derivative CK147 as a translocon inhibitor. A structure of ribosome-Sec61-CK147 reveals CK147 binding the channel and interacting with the plug helix from the lumenal side. The CK147 resistance mutations surround the inhibitor. These structures help in understanding the TRAP functions and provide a new Sec61 site for designing translocon inhibitors.

PubMed: 36867692
DOI: 10.1126/sciadv.adf0797

Experimental method

ELECTRON MICROSCOPY (2.79 Å)