8B5L

Cryo-EM structure of ribosome-Sec61-TRAP (TRanslocon Associated Protein) translocon complex

これはPDB形式変換不可エントリーです。

8B5L の概要

• エントリーDOI: 10.2210/pdb8b5l/pdb
• EMDBエントリー: 15860
• 分子名称: 60S ribosomal protein L35, Ribosomal_L18_c domain-containing protein, 60S ribosomal protein L23, ... (53 entities in total)
• 機能のキーワード: ribosome, sec61, trap, translocon, translation, rna binding protein, eef2, ck147, cada, translocon inhibitor, 80s, 60s, 40s, membrane protein
• 由来する生物種: Oryctolagus cuniculus (rabbit); 詳細
• タンパク質・核酸の鎖数: 51
• 化学式量合計: 2597162.71

構造登録者

Pauwels, E.,Shewakramani, N.R.,De Wijngaert, B.,Vermeire, K.,Das, K. (登録日: 2022-09-23, 公開日: 2023-03-01, 最終更新日: 2023-03-15)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.86 Å)