Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural landscape of the degrading 26S proteasome reveals conformation-specific binding of TXNL1.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 32, Issue 12, Page 2403-2415, Year 2025
Publish date	Nov 6, 2025
Authors	Connor Arkinson / Christine L Gee / Zeyuan Zhang / Ken C Dong / Andreas Martin /
PubMed Abstract	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. ...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. 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 β-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.
External links	Nat Struct Mol Biol / PubMed:41198955 / PubMed Central
Methods	EM (single particle)
Resolution	2.76 - 4.08 Å
Structure data	47719 9e8g EMDB-47719, PDB-9e8g: Nub1/Fat10-processing human 26S proteasome bound to Txnl1 with Rpt5 at top of spiral staircase Method: EM (single particle) / Resolution: 3.01 Å 47720 9e8h EMDB-47720, PDB-9e8h: Human proteasome in resting state conformation bound to TXNL1 in backward conformation Method: EM (single particle) / Resolution: 2.9 Å 47721 9e8i EMDB-47721, PDB-9e8i: Human proteasome in resting state conformation bound to TXNL1 in Forward conformation Method: EM (single particle) / Resolution: 2.87 Å 47722 9e8j EMDB-47722, PDB-9e8j: Nub1/Fat10-processing human 26S proteasome bound to Txnl1 with Rpt1 at top of spiral staircase Method: EM (single particle) / Resolution: 3.47 Å 47723 9e8k EMDB-47723, PDB-9e8k: Nub1/Fat10-processing human 26S proteasome with Rpt6 at top of spiral staircase (AAA+ motor locally refined) Method: EM (single particle) / Resolution: 4.08 Å 47724 9e8l EMDB-47724, PDB-9e8l: Nub1/Fat10-processing human 26S proteasome bound to Txnl1 with Rpt4 at top of spiral staircase Method: EM (single particle) / Resolution: 3.59 Å 47725 9e8n EMDB-47725, PDB-9e8n: Nub1/Fat10-processing human 26S proteasome bound to Txnl1 with Rpt3 at top of spiral staircase (locally refined on the AAA+ motor) Method: EM (single particle) / Resolution: 3.62 Å 47726 9e8o EMDB-47726, PDB-9e8o: Nub1/Fat10-processing human 26S proteasome bound to Txnl1 with Rpt2 at top of spiral staircase and partially unfolded Eos Method: EM (single particle) / Resolution: 3.1 Å 47727 9e8q EMDB-47727, PDB-9e8q: Nub1/Fat10-processing human 26S proteasome with Rpt2 at top of spiral staircase Method: EM (single particle) / Resolution: 3.16 Å 71534 9pdi EMDB-71534, PDB-9pdi: Nub1/Fat10-processing human 26S proteasome with Rpt2 at top of spiral staircase and partially unfolded Eos (AAA+ motor locally refined) Method: EM (single particle) / Resolution: 2.98 Å 71537 9pdl EMDB-71537, PDB-9pdl: Nub1/Fat10-processing human 26S proteasome with Rpt5 at top of spiral staircase (AAA+ locally refined) Method: EM (single particle) / Resolution: 2.76 Å 71538 9pdn EMDB-71538, PDB-9pdn: Nub1/Fat10-processing human 26S proteasome with Rpt1 at top of spiral staircase (AAA+ locally refined) Method: EM (single particle) / Resolution: 3.04 Å EMDB-71581: Nub1/Fat10-processing human 26S proteasome bound to TXNL1 with Rpt3 at top of spiral staircase Method: EM (single particle) / Resolution: 3.49 Å EMDB-71583: NUB1/FAT10-processing human 26S proteasome bound to TXNL1 with Rpt6 at top of spiral staircase Method: EM (single particle) / Resolution: 3.68 Å 71584 9pf1 EMDB-71584, PDB-9pf1: Nub1/Fat10-processing human 26S proteasome with Rpt4 at top of spiral staircase (AAA+ motor locally refined) Method: EM (single particle) / Resolution: 3.57 Å
Chemicals	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-ZN: Unknown entry
Source	homo sapiens (human) lobophyllia hemprichii (invertebrata)
Keywords	MOTOR PROTEIN / HYDROLASE/PROTEIN BINDING / 26S Proteasome / Nub1 / Fat10 / HYDROLASE-PROTEIN BINDING complex