View source for 9pdn


==Nub1/Fat10-processing human 26S proteasome with Rpt1 at top of spiral staircase (AAA+ locally refined)==
<StructureSection load='9pdn' size='340' side='right'caption='[[9pdn]], [[Resolution|resolution]] 3.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9pdn]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PDN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PDN 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]] 3.04&#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>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9pdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pdn OCA], [https://pdbe.org/9pdn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pdn RCSB], [https://www.ebi.ac.uk/pdbsum/9pdn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pdn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PRS8_HUMAN PRS8_HUMAN] The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex.
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== Publication Abstract from PubMed ==
The 26S proteasome targets many cellular proteins for degradation during homeostasis and quality control. Proteasome-interacting cofactors modulate these functions and aid in substrate degradation. Here we solve high-resolution structures of the redox active cofactor TXNL1 bound to the human 26S proteasome at saturating and substoichiometric concentrations by time-resolved cryo-electron microscopy (cryo-EM). We identify distinct binding modes of TXNL1 that depend on the proteasome conformation and ATPase motor states. Together with biophysical and biochemical experiments, we show that the resting-state proteasome binds TXNL1 with low affinity and in variable positions on top of the Rpn11 deubiquitinase. In contrast, in the actively degrading proteasome, TXNL1 uses additional interactions for high-affinity binding, whereby its C-terminal tail covers the catalytic groove of Rpn11 and coordinates the active-site Zn(2+). Furthermore, these cryo-EM structures of the degrading proteasome capture the ATPase hexamer in several spiral-staircase arrangements that indicate temporally asymmetric hydrolysis and conformational changes in bursts during mechanical substrate unfolding and translocation. Remarkably, we catch the proteasome in the act of unfolding the beta-barrel mEos3.2 substrate while the ATPase hexamer is in a particular staircase register. Our findings advance current models for protein translocation through hexameric AAA+ motors and reveal how the proteasome uses its distinct conformational states to coordinate cofactor binding and substrate processing.

Structural landscape of the degrading 26S proteasome reveals conformation-specific binding of TXNL1.,Arkinson C, Gee CL, Zhang Z, Dong KC, Martin A Nat Struct Mol Biol. 2025 Nov 6. doi: 10.1038/s41594-025-01695-2. PMID:41198955<ref>PMID:41198955</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9pdn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arkinson C]]
[[Category: Gee CL]]
[[Category: Martin A]]