7ykt: Difference between revisions

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New page: '''Unreleased structure''' The entry 7ykt is ON HOLD Authors: Description: Category: Unreleased Structures
 
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'''Unreleased structure'''


The entry 7ykt is ON HOLD
==Cryo-EM structure of Drg1 hexamer in helical state treated with ADP/AMPPNP/benzo-diazaborine==
<StructureSection load='7ykt' size='340' side='right'caption='[[7ykt]], [[Resolution|resolution]] 5.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ykt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YKT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YKT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ykt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ykt OCA], [https://pdbe.org/7ykt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ykt RCSB], [https://www.ebi.ac.uk/pdbsum/7ykt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ykt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AFG2_YEAST 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:24371142, PubMed:8109176).<ref>PMID:12006565</ref> <ref>PMID:17646390</ref> <ref>PMID:23185031</ref> <ref>PMID:24371142</ref> <ref>PMID:8109176</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The type II AAA + ATPase Drg1 is a ribosome assembly factor, functioning to release Rlp24 from the pre-60S particle just exported from nucleus, and its activity in can be inhibited by a drug molecule diazaborine. However, molecular mechanisms of Drg1-mediated Rlp24 removal and diazaborine-mediated inhibition are not fully understood. Here, we report Drg1 structures in different nucleotide-binding and benzo-diazaborine treated states. Drg1 hexamers transits between two extreme conformations (planar or helical arrangement of protomers). By forming covalent adducts with ATP molecules in both ATPase domain, benzo-diazaborine locks Drg1 hexamers in a symmetric and non-productive conformation to inhibits both inter-protomer and inter-ring communication of Drg1 hexamers. We also obtained a substrate-engaged mutant Drg1 structure, in which conserved pore-loops form a spiral staircase to interact with the polypeptide through a sequence-independent manner. Structure-based mutagenesis data highlight the functional importance of the pore-loop, the D1-D2 linker and the inter-subunit signaling motif of Drg1, which share similar regulatory mechanisms with p97. Our results suggest that Drg1 may function as an unfoldase that threads a substrate protein within the pre-60S particle.


Authors:  
Structural dynamics of AAA + ATPase Drg1 and mechanism of benzo-diazaborine inhibition.,Ma C, Wu D, Chen Q, Gao N Nat Commun. 2022 Nov 9;13(1):6765. doi: 10.1038/s41467-022-34511-2. PMID:36351914<ref>PMID:36351914</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 7ykt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Chen Q]]
[[Category: Gao N]]
[[Category: Ma CY]]
[[Category: Wu DM]]

Latest revision as of 10:33, 3 July 2024

Cryo-EM structure of Drg1 hexamer in helical state treated with ADP/AMPPNP/benzo-diazaborineCryo-EM structure of Drg1 hexamer in helical state treated with ADP/AMPPNP/benzo-diazaborine

Structural highlights

7ykt is a 6 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 5.9Å
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:24371142, PubMed:8109176).[1] [2] [3] [4] [5]

Publication Abstract from PubMed

The type II AAA + ATPase Drg1 is a ribosome assembly factor, functioning to release Rlp24 from the pre-60S particle just exported from nucleus, and its activity in can be inhibited by a drug molecule diazaborine. However, molecular mechanisms of Drg1-mediated Rlp24 removal and diazaborine-mediated inhibition are not fully understood. Here, we report Drg1 structures in different nucleotide-binding and benzo-diazaborine treated states. Drg1 hexamers transits between two extreme conformations (planar or helical arrangement of protomers). By forming covalent adducts with ATP molecules in both ATPase domain, benzo-diazaborine locks Drg1 hexamers in a symmetric and non-productive conformation to inhibits both inter-protomer and inter-ring communication of Drg1 hexamers. We also obtained a substrate-engaged mutant Drg1 structure, in which conserved pore-loops form a spiral staircase to interact with the polypeptide through a sequence-independent manner. Structure-based mutagenesis data highlight the functional importance of the pore-loop, the D1-D2 linker and the inter-subunit signaling motif of Drg1, which share similar regulatory mechanisms with p97. Our results suggest that Drg1 may function as an unfoldase that threads a substrate protein within the pre-60S particle.

Structural dynamics of AAA + ATPase Drg1 and mechanism of benzo-diazaborine inhibition.,Ma C, Wu D, Chen Q, Gao N Nat Commun. 2022 Nov 9;13(1):6765. doi: 10.1038/s41467-022-34511-2. PMID:36351914[6]

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

References

  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. ↑ Ma C, Wu D, Chen Q, Gao N. Structural dynamics of AAA + ATPase Drg1 and mechanism of benzo-diazaborine inhibition. Nat Commun. 2022 Nov 9;13(1):6765. doi: 10.1038/s41467-022-34511-2. PMID:36351914 doi:http://dx.doi.org/10.1038/s41467-022-34511-2

7ykt, resolution 5.90Å

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