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 AAA+ ATPase motor states in the substrate-degrading human 26S proteasome reveals conformation-specific binding of TXNL1.
Journal, issue, pages	bioRxiv, Year 2024
Publish date	Nov 9, 2024
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 general homeostasis, protein quality control, and the regulation of vital processes. A broad range of proteasome-interacting ...The 26S proteasome targets many cellular proteins for degradation during general homeostasis, protein quality control, and the regulation of vital processes. A broad range of proteasome-interacting cofactors thereby modulates these functions and aids in substrate degradation. Here, we solved several high-resolution structures of the redox active cofactor TXNL1 bound to the human 26S proteasome at saturating and sub-stoichiometric concentrations by time resolved cryo-EM. We identified distinct binding modes of TXNL1 that depend on the proteasome conformational and ATPase motor states. Together with biophysical and biochemical experiments, our structural studies reveal that the resting-state proteasome prior to substrate engagement with the ATPase motor binds TXNL1 with low affinity and in variable positions on top of the Rpn11 deubiquitinase. In contrast, the actively degrading proteasome shows additional interactions leading to high-affinity TXNL1 binding, whereby TXNL1's C-terminal tail covers the catalytic groove of the Rpn11 deubiquitinase and coordinates the active-site Zn. Furthermore, these cryo-EM structures of the degrading proteasome capture the ATPase hexamer in all registers of spiral-staircase arrangements and thus visualize the complete ATP-hydrolysis cycle of the AAA+ motor, indicating 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 spiral staircase register. Our findings challenge current models for protein translocation through hexameric AAA+ motors and reveal how the proteasome uses its distinct but broad range of conformational states to coordinate cofactor binding and substrate processing.
External links	bioRxiv / PubMed:39574680 / PubMed Central
Methods	EM (single particle)
Resolution	2.87 - 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 bound to Txnl1 with Rpt6 at top of spiral staircase 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 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
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