期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 22, 期 11, 页码 914-919出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3112
关键词
-
资金
- Federation of European Biochemical Societies Long Term Fellowship
- Specialist Programme from Bloodwise [12048]
- UK Medical Research Council (MRC) [MC_U105161083, U105115237]
- Wellcome Trust strategic award [100140]
- Wellcome Trust
- MRC
- Tesni Parry Trust
- Ted's Gang
- Cambridge National Institute for Health Research Biomedical Research Centre
- Medical Research Council [MC_U105115237, MC_U105161083, MR/L003368/1] Funding Source: researchfish
- MRC [MR/L003368/1, MC_U105161083, MC_U105115237] Funding Source: UKRI
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据