PSMG1:PSMG2 dimer binds the 20S core particle outer ring

Stable Identifier
R-HSA-9908052
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
3/5
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The PSMG1:PSMG2 heterodimer is a proteasome chaperone that associates with the outer ring of the 20S core particle (20S CP) precursors but not with the mature 20S CP, suggesting that it is released upon maturation of the catalytic active sites (Hirano et al. 2006, reviewed in Tomko and Nochstrasser 2013). Based on cryogenic electron microscopy (cryo-EM), PSMG1:PSMG2 binds the opposite side of the outer ring from the PSMG3:PSMG4 dimer (Adolf et al. 2024). The knockdown of PSGM3 chaperone, needed for the formation of the outer ring, results in accumulation of unbound PSMG1:PSMG2 dimers, implying that PSMG1:PSMG2 dimer binds to pre-formed outer rings (Hirano et al. 2006). The knockdown of PSMG1 and PSMG2 in human embryonic kidney cell line HEK293 leads to accumulation of outer ring dimers, but no inner (beta) rings, suggesting that the PSMG1:PSMG2 dimer functions to prevent the formation of outer ring dimers that might stall proper proteasome biogenesis (Hirano et al. 2006, reviewed in Tomko and Hochstrasser 2013). By cryo-EM, PSMG1:PSMG2 contacts all the alpha (PSMA) subuits of the outer ring except alpha-3 (PSMA4), directly binding N-termini from multiple PSMAs (Adolf et al. 2024).
Literature References
PubMed ID Title Journal Year
17189198 Cooperation of multiple chaperones required for the assembly of mammalian 20S proteasomes

Hirano, Y, Hayashi, H, Iemura, S, Hendil, KB, Niwa, S, Kishimoto, T, Kasahara, M, Natsume, T, Tanaka, K, Murata, S

Mol Cell 2006
38600324 Visualizing chaperone-mediated multistep assembly of the human 20S proteasome

Adolf, F, Du, J, Goodall, EA, Walsh, RM, Rawson, S, von Gronau, S, Harper, JW, Hanna, J, Schulman, BA

Nat Struct Mol Biol 2024
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