Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1.

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Grishkovskaya, Irina  ORCID logo
Hodirnau, Victor-Valentin  ORCID logo
Hetzmannseder, Christina 
Zisser, Gertrude 

The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large ribosomal subunit. Drg1 releases the shuttling maturation factor Rlp24 from pre-60S particles shortly after nuclear export, a strict requirement for downstream maturation. The molecular mechanism of release remained elusive. Here, we report a series of cryo-EM structures that captured the extraction of Rlp24 from pre-60S particles by Saccharomyces cerevisiae Drg1. These structures reveal that Arx1 and the eukaryote-specific rRNA expansion segment ES27 form a joint docking platform that positions Drg1 for efficient extraction of Rlp24 from the pre-ribosome. The tips of the Drg1 N domains thereby guide the Rlp24 C terminus into the central pore of the Drg1 hexamer, enabling extraction by a hand-over-hand translocation mechanism. Our results uncover substrate recognition and processing by Drg1 step by step and provide a comprehensive mechanistic picture of the conserved modus operandi of AAA-ATPases.

ATPases Associated with Diverse Cellular Activities, Adenosine Triphosphatases, Ribosomal Proteins, Ribosome Subunits, Large, Eukaryotic, Ribosomes, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
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Nat Struct Mol Biol
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Springer Science and Business Media LLC
MRC (MR/T012412/1)