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TitleStructure and assembly pathway of the ribosome quality control complex.
Journal, issue, pagesMol Cell, Vol. 57, Issue 3, Page 433-444, Year 2015
Publish dateFeb 5, 2015
AuthorsSichen Shao / Alan Brown / Balaji Santhanam / Ramanujan S Hegde /
PubMed AbstractDuring ribosome-associated quality control, stalled ribosomes are split into subunits and the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin. How this low-abundance ubiquitin ...During ribosome-associated quality control, stalled ribosomes are split into subunits and the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin. How this low-abundance ubiquitin ligase targets rare stall-generated 60S among numerous empty 60S is unknown. Here, we show that Listerin specificity for nascent chain-60S complexes depends on nuclear export mediator factor (NEMF). The 3.6 Å cryo-EM structure of a nascent chain-containing 60S-Listerin-NEMF complex revealed that NEMF makes multiple simultaneous contacts with 60S and peptidyl-tRNA to sense nascent chain occupancy. Structural and mutational analyses showed that ribosome-bound NEMF recruits and stabilizes Listerin's N-terminal domain, while Listerin's C-terminal RWD domain directly contacts the ribosome to position the adjacent ligase domain near the nascent polypeptide exit tunnel. Thus, highly specific nascent chain targeting by Listerin is imparted by the avidity gained from a multivalent network of context-specific individually weak interactions, highlighting a new principle of client recognition during protein quality control.
External linksMol Cell / PubMed:25578875 / PubMed Central
MethodsEM (single particle)
Resolution3.6 Å
Structure data

2832

3j92

EMDB-2832: Cryo-EM map of a mammalian 60S ribosome-nascent chain-tRNA complex with Listerin and NEMF
PDB-3j92: Structure and assembly pathway of the ribosome quality control complex
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • oryctolagus cuniculus (rabbit)
  • sus scrofa (pig)
  • unidentified (others)
  • homo sapiens (human)
KeywordsRIBOSOME/LIGASE / RWD / RING / quality control / RIBOSOME-LIGASE complex

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