Reactome | Formation of the inner ring of the 20S core particle of the 26S proteasome

Formation of the inner ring of the 20S core particle of the 26S proteasome

Stable Identifier

R-HSA-9907898

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

3/5

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Formation of the inner ring of the 20S core particle of the 26S proteasome

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The inner ring of 20S core particle (20S CP) of 26S proteasome is formed by association of seven distinct beta-subunits (beta1–beta7, officially PSMB1-7 in humans, where beta-1 corresponds to PSMB6, beta-2 to PSMB7, beta-3 to PSMB3, beta-4 to PSMB2, beta-5 to PSMB5, beta-6 to PSMB1, and beta-7 to PSMB4) (Hirano et al. 2006, reviewed in Tomko and Hochstrasser 2013). PSMB5 (beta-5), PSMB6 (beta-1), and PSMB7 (beta-2) subunits contain the proteolytic active sites (reviewed in Tomko and Hochstrasser 2013). Beta subunits assemble onto the inner surface of the pre-formed outer ring consisting of alpha subunits (PSMAs) (Hirano et al. 2006). POMP (UMP1) protein, which binds to the outer ring, plays an important role in initiation of the inner ring assembly (Hirano et al. 2006). By using precursor complex-specific antibodies to isolate 20S CP precursors from human cervical carcinoma cell line HeLa, it was shown that the main steps in the 20S core complex formation take place at the endoplasmic reticulum (ER), which is directed by POMP (Fricke et al. 2007). POMP interacts with ER membranes, binds to the outer ring, recruits beta-subunits stepwise, and mediates the association of mammalian precursor complexes with the ER (Fricke et al. 2007). By systematic siRNA-mediated knockdown of beta subunits of the inner ring in human embryonic kidney cell line HEK293T (Hirano et al. 2008) and by cryogenic electron microscopy (cryo-EM) of human 20S CP intermediates (Adolf et al. 2024), it was determined that the addition of beta subunits begins with beta-2 (PSMB7), which loads either after POMP or together with POMP. Formation of the inner ring then proceeds in a defined order of beta-3 (PSMB3), beta-4 (PSMB2), beta-5 (PSMB5), beta-6 (PSMB1), beta-1 (PSMB6), and finally beta-7 (PSMB4) (Hirano et al. 2008; Adolf et al. 2024; reviewed in Tomko and Hockstrasser 2013).

Literature References

PubMed ID	Title	Journal	Year
17948026	The proteasome maturation protein POMP facilitates major steps of 20S proteasome formation at the endoplasmic reticulum Fricke, B, Heink, S, Steffen, J, Kloetzel, PM, Krüger, E	EMBO Rep	2007
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
18650933	Dissecting beta-ring assembly pathway of the mammalian 20S proteasome Hirano, Y, Kaneko, T, Okamoto, K, Bai, M, Yashiroda, H, Furuyama, K, Kato, K, Tanaka, K, Murata, S	EMBO J	2008
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