Literature / Library / Proteasome

Proteasome

Four stacked rings of seven subunits each, capped at both ends, carrying three different cutting specificities in one machine.

10 pictures and 6 papers. Its organelle page: Proteasome.

Gallery

Three major conformational states of the 26S proteasome determined by electron cryomicroscopy. The copy beside this is shown in one fixed conformation; the complex actually moves between states, and that motion is what this figure is about.

FridoFoe · CC BY-SA 3.0

Bafilomycin-induced expression of degradation markers. Green - Cx36-GFP, red - specific marker (RAB11A, PSMA1, p62), blue - DAPI.

Katan, Mróz, Pacwa et al 2026, Acta Biochimica Polonica · CC BY 4.0

Human sperm nuclear lacunae are variable in size and positive for proteasomes with testis-specific subunit PSMA8, which segregates from DNA. a, A z slice of 3D reconstructed cryo-SEM volumetric data of human sperm cells. Sperm lacunae are visible in the nucleus. Scale bar, 1 μm. b, Detail of three human sperm heads from volumetric data shown in a. Segmented lacunae are shown in color (yellow, green and blue) at three different z heights. The sperm nucleus is shown in dashed black lines. Scale bars, 1 μm. c, Relative frequency plot of the Feret diameters of segmented human sperm lacunae (blue) and comparison to values from mouse data (red). d, Violin plots for data shown in c. e, STORM of sperm-specific proteasome subunit α4s (PSMA8) in human sperm cells. The white dashed line shows the sperm nuclear region. Right: α4s cluster identification following DBSCAN analysis of α4s within nuclear region. f, Histogram of α4s clusters identified using STORM in human (blue) and mouse (red) cells. g, Violin plots for data shown in f. h, STORM imaging of DNA and α4s in a human sperm cell, using SiR–DNA and immunofluorescence staining against α4s. Regions of α4s density segregated from DNA are shown within dashed yellow lines in the rightmost panel. Scale bar, 1 μm. i, SIM showing proteasome subunit PSMB7 (β2) forming foci in the nucleus of sperm cells (magenta) in regions of no DNA staining (Hoechst). Scale bar, 5 μm. j, SIM imaging of human sperm cells showing nuclear foci of α4/α4s (PSMA7/8) proteasome subunit (green) and partial colocalization with PA200 (magenta). Small α4/α4s foci were also present in the tail. Scale bar, 5 μm.

Kolata, dos Santos, Knowles et al 2026, Nature Structural and Molecular Biology. Fig. 2 · CC BY 4.0

RPN-6.1 and RPN-7 are required for the nuclear localization of RPN-8 and RPN-9. (A) Live imaging of hermaphrodite oocytes from endogenously GFP tagged strains rpn-7[ana1(gfp::rpn7)], rpn-8[ana4(gfp::rpn-8)], rpn-9[ana5(gfp::rpn-9)] and rpn-12[ana6(gfp::rpn-12)] treated with either control(RNAi), rpn-6.1(RNAi) or rpn-7(RNAi) (n = 15-42). Scale bar represents 25 um.

Fernando, Quesada-Candela, Murray et al 2022, Frontiers in Cell and Developmental Biology · CC BY 4.0

Mapping of the PIR domain. (A) Immunofluorescence images of HeLa p62KO cells transfected with FLAG-tagged constructs: p62-PB1 (1-115), p62WT, and p62DeltaPB1 (Delta1-123). Cells were co-stained with antibodies against FLAG (green) and the proteasome alpha6 subunit (red). Scale bars: 20 um. (B) Immunofluorescence images of HeLa p62KO cells expressing N-terminal deletion variants of p62. Cells were co-stained for FLAG (green) and the proteasome alpha6 subunit (red). Scale bars: 30 um. In all panels, arrows point to p62 foci.

Lipskerov, Cohen-Kaplan, Ciechanover et al 2026, Cells · CC BY 4.0

Nuclear lacunae in human sperm cells are proteasomal compartments. a, Cryo-EM low-magnification lamellae map showing four human sperm heads. Rectangles indicate regions with sperm lacunae targeted for tilt-series acquisition. The image is representative of >8 independent experiments, using samples from >10 donors. Scale bar, 1 um. P-DNA, protamine-DNA. b, z slices from reconstructed tomograms showing barrel-shaped protein complexes inside membraneless nuclear compartments. Scale bars, 100 nm. c, Zoomed-in regions from tomograms showing barrel-shaped particles corresponding to 20S, 20S-PA200 and PA200-20S-PA200 inside lacunae. Scale bar, 100 nm.

Kolata, dos Santos, Knowles et al 2026, Nature Structural and Molecular Biology · CC BY 4.0

Bafilomycin-induced expression of degradation markers. Green - Cx36-GFP, red - specific marker (RAB11A, PSMA1, p62), blue - DAPI.

Katan, Mróz, Pacwa et al 2026, Acta Biochimica Polonica · CC BY 4.0

Proteasome distribution and clustering in mouse and human sperm cells. e , SIM image showing localisation of the AAA-ATPase subunit of 19S, PSMC1 (magenta) in the tail of human sperm cells. Scale bar = 10 um. Image is representative of >20 cells (2 biological replicates).

Kolata, dos Santos, Knowles et al 2026, Nature Structural & Molecular Biology · CC BY 4.0

Gallery of lacunae and subtomogram averaging processing pipeline of nuclear sperm proteasomes. a, cryo-tomographic slices from deconvolved tomograms of six nuclear lacunae filled with barrel-shaped proteins. Scale bar = 100 nm. b, Details of the subtomogram averaging processing pipeline of 20S, 20S-PA200 and PA200-20S-PA200 proteasomes. Subtomogram averages with fitted PDBs are shown. c, Gold-standard Fourier Shell Correlation (FSC) curves for the Subtomogram Averaging (STA) maps: 20S, 20S-PA200 and PA200-20S-PA200. The resolution values at FSC = 0.143 (half-map FSC) are indicated. (human (sperm cell nuclear lacunae); Extended Data Fig. 1, a (cryo-tomographic slices, six nuclear lacunae; rows 31-517, cols 41-1371 of figure).)

Kolata, dos Santos, Knowles et al 2026, Nature Structural & Molecular Biology · CC BY 4.0

Bafilomycin-induced expression of degradation markers. Green - Cx36-GFP, red - specific marker (RAB11A, PSMA1, p62), blue - DAPI. (mouse (661W photoreceptor cells, Cx36-GFP transfected); FIGURE 5, full figure (three-row IF panel showing RAB11A, PSMA1, and p62 co-staining with Cx36-GFP; white header trimmed).)

Katan, Mróz, Pacwa et al 2026, Acta Biochimica Polonica · CC BY 4.0

Papers

  1. Hermens J, Lucke L, Pieles O, Maier O, Othmen H, Burghardt T, et al. Proteasome inhibition alleviates proteinuria in Lmx1b knock-in mice with dysfunctional LIM domains. Nat Commun. 2026;17:9731. PMID: 42722687.
  2. Kolata P, Dos Santos , Knowles O, Dendooven T, Allegretti M. Molecular architecture and spatial organization of proteasomes in the human sperm nucleus. Nat Struct Mol Biol. 2026;33:1367-1380. PMID: 42680909.
  3. Katan M, Mróz K, Pacwa A, Lewin-Kowalik J, Smędowski A. Gap junction protein connexin 36 proteostatic mechanisms in photoreceptor cells subjected to excitotoxic stress. Acta Biochim Pol. 2026;73:16091. PMID: 42666667.
  4. Lee CY, Han S, Haertle L, Munawar U, Vogt C, Streubel J, et al. Proteome Profiling Reveals NQO2 Activity Contributing to Proteasome Inhibitor Resistance in Multiple Myeloma Cell Lines. Mol Cell Proteomics. 2026;25:101615. PMID: 42362189.
  5. Labrador M, Cozzubbo S, Porro M, Cumerlato M, Bandini C, Mereu E, et al. MDM2 Drives Proteasome Inhibitor Resistance and Represents a TP53-Independent Therapeutic Vulnerability in Multiple Myeloma. Cells. 2026;15:831. PMID: 42121932.
  6. Navon A, Ciechanover A. The 26 S proteasome: from basic mechanisms to drug targeting. J Biol Chem. 2009;284:33713-8. PMID: 19812037.

cytology · hub