6QKL

Mechanism of eIF6 release from the nascent 60S ribosomal subunit

Summary for 6QKL

• Entry DOI: 10.2210/pdb6qkl/pdb
• EMDB information: 3145
• Descriptor: 26S RIBOSOMAL RNA, 60S acidic ribosomal protein P0, 60S ribosomal protein L12, ... (11 entities in total)
• Functional Keywords: 60s subunit, eif6, sbds, ul16, ribosome
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 11
• Total formula weight: 1419237.61

Authors

Kargas, V.,Warren, A.J. (deposition date: 2019-01-29, release date: 2019-03-20, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.3 Å)