5AN9
Mechanism of eIF6 release from the nascent 60S ribosomal subunit
Summary for 5AN9
| Entry DOI | 10.2210/pdb5an9/pdb |
| Related | 5ANB 5ANC |
| EMDB information | 3145 3146 3147 |
| Descriptor | 60S RIBOSOMAL PROTEIN L3, RIBOSOME MATURATION PROTEIN SBDS, 26S RIBOSOMAL RNA, ... (11 entities in total) |
| Functional Keywords | translation, ribosomopathy, efl1, gtpase, ribosome biogenesis |
| Biological source | HOMO SAPIENS (HUMAN) More |
| Cellular location | Cytoplasm: P34113 Q9Y3A5 Q551M2 Ubiquitin: Cytoplasm . 60S ribosomal protein L40: Cytoplasm : P14794 |
| Total number of polymer chains | 11 |
| Total formula weight | 1419237.61 |
| Authors | Weis, F.,Giudice, E.,Churcher, M.,Jin, L.,Hilcenko, C.,Wong, C.C.,Traynor, D.,Kay, R.R.,Warren, A.J. (deposition date: 2015-09-06, release date: 2015-10-21, Last modification date: 2024-05-08) |
| 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-, 2015 Cited by 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: 26479198DOI: 10.1038/NSMB.3112 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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