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TitleFunctionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 6789, Year 2021
Publish dateNov 23, 2021
AuthorsPatrick R Smith / Sarah Loerch / Nikesh Kunder / Alexander D Stanowick / Tzu-Fang Lou / Zachary T Campbell /
PubMed AbstractProcessing bodies (p-bodies) are a prototypical phase-separated RNA-containing granule. Their abundance is highly dynamic and has been linked to translation. Yet, the molecular mechanisms responsible ...Processing bodies (p-bodies) are a prototypical phase-separated RNA-containing granule. Their abundance is highly dynamic and has been linked to translation. Yet, the molecular mechanisms responsible for coordinate control of the two processes are unclear. Here, we uncover key roles for eEF2 kinase (eEF2K) in the control of ribosome availability and p-body abundance. eEF2K acts on a sole known substrate, eEF2, to inhibit translation. We find that the eEF2K agonist nelfinavir abolishes p-bodies in sensory neurons and impairs translation. To probe the latter, we used cryo-electron microscopy. Nelfinavir stabilizes vacant 80S ribosomes. They contain SERBP1 in place of mRNA and eEF2 in the acceptor site. Phosphorylated eEF2 associates with inactive ribosomes that resist splitting in vitro. Collectively, the data suggest that eEF2K defines a population of inactive ribosomes resistant to recycling and protected from degradation. Thus, eEF2K activity is central to both p-body abundance and ribosome availability in sensory neurons.
External linksNat Commun / PubMed:34815424 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.3 Å
Structure data

23500

7ls1

EMDB-23500, PDB-7ls1:
80S ribosome from mouse bound to eEF2 (Class II)
Method: EM (single particle) / Resolution: 3.3 Å

23501

7ls2

EMDB-23501, PDB-7ls2:
80S ribosome from mouse bound to eEF2 (Class I)
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-HOH:
WATER

Source
  • mus musculus (house mouse)
  • Mouse (mice)
KeywordsRIBOSOME / regulation / translation

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