6QKL

Mechanism of eIF6 release from the nascent 60S ribosomal subunit

6QKL の概要

• エントリーDOI: 10.2210/pdb6qkl/pdb
• EMDBエントリー: 3145
• 分子名称: 26S RIBOSOMAL RNA, 60S acidic ribosomal protein P0, 60S ribosomal protein L12, ... (11 entities in total)
• 機能のキーワード: 60s subunit, eif6, sbds, ul16, ribosome
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 1419237.61

構造登録者

Kargas, V.,Warren, A.J. (登録日: 2019-01-29, 公開日: 2019-03-20, 最終更新日: 2024-11-13)

主引用文献

Weis, F.,Giudice, E.,Churcher, M.,Jin, L.,Hilcenko, C.,Wong, C.C.,Traynor, D.,Kay, R.R.,Warren, A.J.
Mechanism of eIF6 release from the nascent 60S ribosomal subunit.
Nat.Struct.Mol.Biol., 22:914-919, 2015

PubMed Abstract: SBDS protein (deficient in the inherited leukemia-predisposition disorder Shwachman-Diamond syndrome) and the GTPase EFL1 (an EF-G homolog) activate nascent 60S ribosomal subunits for translation by catalyzing eviction of the antiassociation factor eIF6 from nascent 60S ribosomal subunits. However, the mechanism is completely unknown. Here, we present cryo-EM structures of human SBDS and SBDS-EFL1 bound to Dictyostelium discoideum 60S ribosomal subunits with and without endogenous eIF6. SBDS assesses the integrity of the peptidyl (P) site, bridging uL16 (mutated in T-cell acute lymphoblastic leukemia) with uL11 at the P-stalk base and the sarcin-ricin loop. Upon EFL1 binding, SBDS is repositioned around helix 69, thus facilitating a conformational switch in EFL1 that displaces eIF6 by competing for an overlapping binding site on the 60S ribosomal subunit. Our data reveal the conserved mechanism of eIF6 release, which is corrupted in both inherited and sporadic leukemias.

PubMed: 26479198
DOI: 10.1038/nsmb.3112

実験手法

ELECTRON MICROSCOPY (3.3 Å)