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TitleMechanism of eIF6 release from the nascent 60S ribosomal subunit.
Journal, issue, pagesNat Struct Mol Biol, Vol. 22, Issue 11, Page 914-919, Year 2015
Publish dateOct 19, 2015
AuthorsFélix Weis / Emmanuel Giudice / Mark Churcher / Li Jin / Christine Hilcenko / Chi C Wong / David Traynor / Robert R Kay / Alan J Warren /
PubMed AbstractSBDS 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 ...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.
External linksNat Struct Mol Biol / PubMed:26479198 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 4.2 Å
Structure data

3145

5an9

6qkl

EMDB-3145, PDB-5an9, PDB-6qkl:
Mechanism of eIF6 release from the nascent 60S ribosomal subunit
Method: EM (single particle) / Resolution: 3.3 Å

3146

5anb

EMDB-3146, PDB-5anb:
Mechanism of eIF6 release from the nascent 60S ribosomal subunit
Method: EM (single particle) / Resolution: 4.1 Å

3147

5anc

EMDB-3147, PDB-5anc:
Mechanism of eIF6 release from the nascent 60S ribosomal subunit
Method: EM (single particle) / Resolution: 4.2 Å

Source
  • dictyostelium discoideum (eukaryote)
  • homo sapiens (human)
KeywordsTRANSLATION / RIBOSOMOPATHY / EFL1 / GTPASE / RIBOSOME BIOGENESIS / RIBOSOME / 60S subunit / eIF6 / SBDS / uL16

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