7z34

Structure of pre-60S particle bound to DRG1(AFG2)Structure of pre-60S particle bound to DRG1(AFG2)

Structural highlights

7z34 is a 15 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.8Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AFG2_YEAST ATP-dependent chaperone which uses the energy provided by ATP hydrolysis to generate mechanical force to disassemble protein complexes (PubMed:12006565, PubMed:17646390, PubMed:23185031, PubMed:24371142). Plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RLP24 from the pre-ribosomal particles (PubMed:17646390, PubMed:23185031, PubMed:24371142). This step facilitates the subsequent release of other shuttling proteins such as NOG1 and allows the transition of the pre-ribosomal particles to later maturation forms that bind REI1 (PubMed:17646390, PubMed:23185031, PubMed:24371142). Essential for viability (PubMed:8109176, PubMed:24371142).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

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.

Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1.,Prattes M, Grishkovskaya I, Hodirnau VV, Hetzmannseder C, Zisser G, Sailer C, Kargas V, Loibl M, Gerhalter M, Kofler L, Warren AJ, Stengel F, Haselbach D, Bergler H Nat Struct Mol Biol. 2022 Sep 12. pii: 10.1038/s41594-022-00832-5. doi:, 10.1038/s41594-022-00832-5. PMID:36097293^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zakalskiy A, Hogenauer G, Ishikawa T, Wehrschutz-Sigl E, Wendler F, Teis D, Zisser G, Steven AC, Bergler H. Structural and enzymatic properties of the AAA protein Drg1p from Saccharomyces cerevisiae. Decoupling of intracellular function from ATPase activity and hexamerization. J Biol Chem. 2002 Jul 26;277(30):26788-95. doi: 10.1074/jbc.M201515200. Epub 2002, May 10. PMID:12006565 doi:http://dx.doi.org/10.1074/jbc.M201515200
↑ Pertschy B, Saveanu C, Zisser G, Lebreton A, Tengg M, Jacquier A, Liebminger E, Nobis B, Kappel L, van der Klei I, Hogenauer G, Fromont-Racine M, Bergler H. Cytoplasmic recycling of 60S preribosomal factors depends on the AAA protein Drg1. Mol Cell Biol. 2007 Oct;27(19):6581-92. doi: 10.1128/MCB.00668-07. Epub 2007 Jul , 23. PMID:17646390 doi:http://dx.doi.org/10.1128/MCB.00668-07
↑ Kappel L, Loibl M, Zisser G, Klein I, Fruhmann G, Gruber C, Unterweger S, Rechberger G, Pertschy B, Bergler H. Rlp24 activates the AAA-ATPase Drg1 to initiate cytoplasmic pre-60S maturation. J Cell Biol. 2012 Nov 26;199(5):771-82. doi: 10.1083/jcb.201205021. PMID:23185031 doi:http://dx.doi.org/10.1083/jcb.201205021
↑ Loibl M, Klein I, Prattes M, Schmidt C, Kappel L, Zisser G, Gungl A, Krieger E, Pertschy B, Bergler H. The drug diazaborine blocks ribosome biogenesis by inhibiting the AAA-ATPase Drg1. J Biol Chem. 2014 Feb 14;289(7):3913-22. doi: 10.1074/jbc.M113.536110. Epub 2013 , Dec 26. PMID:24371142 doi:http://dx.doi.org/10.1074/jbc.M113.536110
↑ Thorsness PE, White KH, Ong WC. AFG2, an essential gene in yeast, encodes a new member of the Sec18p, Pas1p, Cdc48p, TBP-1 family of putative ATPases. Yeast. 1993 Nov;9(11):1267-71. PMID:8109176 doi:http://dx.doi.org/10.1002/yea.320091114
↑ Prattes M, Grishkovskaya I, Hodirnau VV, Hetzmannseder C, Zisser G, Sailer C, Kargas V, Loibl M, Gerhalter M, Kofler L, Warren AJ, Stengel F, Haselbach D, Bergler H. Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1. Nat Struct Mol Biol. 2022 Sep 12. pii: 10.1038/s41594-022-00832-5. doi:, 10.1038/s41594-022-00832-5. PMID:36097293 doi:http://dx.doi.org/10.1038/s41594-022-00832-5

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OCA

[1] Zakalskiy A, Hogenauer G, Ishikawa T, Wehrschutz-Sigl E, Wendler F, Teis D, Zisser G, Steven AC, Bergler H. Structural and enzymatic properties of the AAA protein Drg1p from Saccharomyces cerevisiae. Decoupling of intracellular function from ATPase activity and hexamerization. J Biol Chem. 2002 Jul 26;277(30):26788-95. doi: 10.1074/jbc.M201515200. Epub 2002, May 10. PMID:12006565 doi:http://dx.doi.org/10.1074/jbc.M201515200

[2] Pertschy B, Saveanu C, Zisser G, Lebreton A, Tengg M, Jacquier A, Liebminger E, Nobis B, Kappel L, van der Klei I, Hogenauer G, Fromont-Racine M, Bergler H. Cytoplasmic recycling of 60S preribosomal factors depends on the AAA protein Drg1. Mol Cell Biol. 2007 Oct;27(19):6581-92. doi: 10.1128/MCB.00668-07. Epub 2007 Jul , 23. PMID:17646390 doi:http://dx.doi.org/10.1128/MCB.00668-07

[3] Kappel L, Loibl M, Zisser G, Klein I, Fruhmann G, Gruber C, Unterweger S, Rechberger G, Pertschy B, Bergler H. Rlp24 activates the AAA-ATPase Drg1 to initiate cytoplasmic pre-60S maturation. J Cell Biol. 2012 Nov 26;199(5):771-82. doi: 10.1083/jcb.201205021. PMID:23185031 doi:http://dx.doi.org/10.1083/jcb.201205021

[4] Loibl M, Klein I, Prattes M, Schmidt C, Kappel L, Zisser G, Gungl A, Krieger E, Pertschy B, Bergler H. The drug diazaborine blocks ribosome biogenesis by inhibiting the AAA-ATPase Drg1. J Biol Chem. 2014 Feb 14;289(7):3913-22. doi: 10.1074/jbc.M113.536110. Epub 2013 , Dec 26. PMID:24371142 doi:http://dx.doi.org/10.1074/jbc.M113.536110

[5] Thorsness PE, White KH, Ong WC. AFG2, an essential gene in yeast, encodes a new member of the Sec18p, Pas1p, Cdc48p, TBP-1 family of putative ATPases. Yeast. 1993 Nov;9(11):1267-71. PMID:8109176 doi:http://dx.doi.org/10.1002/yea.320091114

[6] Prattes M, Grishkovskaya I, Hodirnau VV, Hetzmannseder C, Zisser G, Sailer C, Kargas V, Loibl M, Gerhalter M, Kofler L, Warren AJ, Stengel F, Haselbach D, Bergler H. Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1. Nat Struct Mol Biol. 2022 Sep 12. pii: 10.1038/s41594-022-00832-5. doi:, 10.1038/s41594-022-00832-5. PMID:36097293 doi:http://dx.doi.org/10.1038/s41594-022-00832-5

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