7wd3: Difference between revisions
New page: '''Unreleased structure''' The entry 7wd3 is ON HOLD Authors: Ma, C.Y., Wu, D.M., Chen, Q., Gao, N. Description: Cryo-EM structure of Drg1 in the presence of ATP/diazaborine [[Category... |
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The | ==Cryo-EM structure of Drg1 hexamer treated with ATP and benzo-diazaborine== | ||
<StructureSection load='7wd3' size='340' side='right'caption='[[7wd3]], [[Resolution|resolution]] 3.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7wd3]] 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=7WD3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WD3 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=NDT:2-(TOLUENE-4-SULFONYL)-2H-BENZO[D][1,2,3]DIAZABORININ-1-OL'>NDT</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=7wd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wd3 OCA], [https://pdbe.org/7wd3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wd3 RCSB], [https://www.ebi.ac.uk/pdbsum/7wd3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wd3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A6A5PRU8_YEASX A0A6A5PRU8_YEASX] | |||
<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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7wd3" style="background-color:#fffaf0;"></div> | ||
[[Category: Gao | == References == | ||
[[Category: | <references/> | ||
[[Category: Wu | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae]] | |||
[[Category: Chen Q]] | |||
[[Category: Gao N]] | |||
[[Category: Ma CY]] | |||
[[Category: Wu DM]] | |||
Latest revision as of 13:03, 14 December 2022
Cryo-EM structure of Drg1 hexamer treated with ATP and benzo-diazaborineCryo-EM structure of Drg1 hexamer treated with ATP and benzo-diazaborine
Structural highlights
FunctionPublication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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