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 dynamics of the midnolin-proteasome during ubiquitin-independent substrate turnover.
Journal, issue, pages	Nat Commun, Vol. 17, Issue 1, Year 2026
Publish date	Mar 27, 2026
Authors	Chuanda Zhu / Lu Qin / Zonglin Dai / Peng Zuo / Ao Yang / Lijun Zhong / Zhiqiang Lin / Ling Liang /
PubMed Abstract	The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein ...The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein midnolin, yet its molecular mechanism remains poorly understood. Here, we present nine cryo-electron microscopy structures of the human 26S proteasome in complex with midnolin, which collectively delineate a near-complete catalytic cycle. Our structures reveal that midnolin binds to the proteasome via the RPN1 subunit by its C-terminal helix. Unexpectedly, its ubiquitin-like domain interacts with the RPN11 deubiquitinase in a non-catalytic role. This interaction positions the adjacent Catch domain, which is responsible for substrate binding, directly above the proteasomal entrance, potentially facilitating substrate entry into the proteasome. Furthermore, we observe four consecutive spiral staircase conformations of the AAA+ ATPase hexamer during substrate translocation. These findings provide insights into the mechanisms underlying ubiquitin-independent nuclear protein degradation and may help develop strategies for targeting nuclear proteins via direct proteasomal degradation.
External links	Nat Commun / PubMed:41896529 / PubMed Central
Methods	EM (single particle)
Resolution	2.75 - 4.23 Å
Structure data	EMDB-63725: Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral staircase Method: EM (single particle) / Resolution: 3.34 Å EMDB-63726: Consensus map of substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral staircase Method: EM (single particle) / Resolution: 2.75 Å EMDB-63727: Consensus map of substrate-engaged human 26S proteasome bound to midnolin with RPT5 at top of spiral staircase Method: EM (single particle) / Resolution: 2.93 Å EMDB-63728: Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT5 at top of spiral staircase Method: EM (single particle) / Resolution: 3.44 Å EMDB-63751: Consensus map of substrate-engaged human 26S proteasome bound to midnolin with RPT2 at top of spiral staircase Method: EM (single particle) / Resolution: 2.91 Å EMDB-63752: Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT2 at top of spiral staircase Method: EM (single particle) / Resolution: 3.5 Å 63775 9mbo EMDB-63775, PDB-9mbo: Focused refinement of RPN1 and the C-terminal helix of midnolin in the substrate-engaged human 26S proteasome Method: EM (single particle) / Resolution: 2.83 Å 63776 9mbp EMDB-63776, PDB-9mbp: Substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral staircase Method: EM (single particle) / Resolution: 2.75 Å 63777 9mbq EMDB-63777, PDB-9mbq: Substrate-engaged human 26S proteasome bound to midnolin with RPT5 at top of spiral staircase Method: EM (single particle) / Resolution: 3.08 Å 63817 9u3l EMDB-63817, PDB-9u3l: Substrate-engaged human 26S proteasome bound to midnolin with RPT2 at top of spiral staircase Method: EM (single particle) / Resolution: 2.91 Å 63850 9u4m EMDB-63850, PDB-9u4m: Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT6 at top of spiral staircase Method: EM (single particle) / Resolution: 4.14 Å 63943 9u7r EMDB-63943, PDB-9u7r: Substrate-free human 26S proteasome purified by midnolin, 20S proteasome, RPTs and RPN11 part Method: EM (single particle) / Resolution: 3.17 Å 65595 9w39 EMDB-65595, PDB-9w39: Structure of human 26S proteasome complexed with midnolin, 19S proteasome with Ubl bound Method: EM (single particle) / Resolution: 3.65 Å 65839 9wbg EMDB-65839, PDB-9wbg: Structure of human 26S proteasome complexed with midnolin, 19S proteasome with Ubl and Catch domain resolved Method: EM (single particle) / Resolution: 4.23 Å 68472 22mm EMDB-68472, PDB-22mm: Structure of human 26S proteasome complexed with midnolin(1-111+337-468) Method: EM (single particle) / Resolution: 3.42 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-LDZ: N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-4-methyl-1-oxopentan-2-yl]-L-leucinamide
Source	homo sapiens (human) purpureocillium lilacinum (fungus) pseudotamlana agarivorans (bacteria) synthetic construct (others) escherichia coli str. k-12 substr. mg1655 (bacteria) escherichia coli k-12 (bacteria)
Keywords	HYDROLASE / 26S proteasome / midnolin / Complex / proteasome