Molecular Structures of 20S and 26S Proteasomes

Abstract

Eukaryotic proteasomes are unusually large protein complexes with characteristic sets of subunits and have been classified into two isoforms with apparent sedimentation coefficients of 20S and 26S, respectively. The 20S proteasome (previously named the multicatalytic proteinase complex) is a cylindrical particle with a molecular weight (MW) of approximately 750 kD. It is a dimeric assembly of two symmetrical discs, each consisting of 7 α-type subunits and 7 ß-type subunits, having the molecular organization an[1-7)ßn[1-7)ßn[1-7)an[1-7), where 'n' indicates the number of heterogeneous 7 subunits with MWs of 21-32 kD. The α-type and ß-type subunits constitute a unique multi-gene family encoding previously unidentified, but homologous, polypeptides that have been conserved during evolution. Interestingly, some ß-type subunits with catalytic functions appear to be replaced by very homologous, but distinct, gene products that might be generated by gene duplication in response to extracellular signals, such as γ-interferon, suggesting that the 20S proteasome exists in cells as a heterogeneous population with functional diversity. The 26S proteasome is a eukaryotic ATP-dependent protease, selectively degrading various cellular proteins with specific degradation signals such as a multi-ubiquitin chain. It is a cylindrical caterpillar-shaped complex with a MW of about 2,000 kD. The 26S proteasome is a symmetrical assembly of a central 20S proteasome and a large terminal polypeptide complex with an apparent sedimentation coefficient of 22S. The terminal 22S subset consists of multiple components with MWs of 30-110 kD, which possibly have regulatory functions, and contains multiple ATPases, a de-ubiquitinating enzyme and the recognition molecule(s) for the target proteins. Thus the 26S proteasome is a multi-molecular assembly, consisting of the 20S proteasome and the 22S regulatory subunit complex.

Plant 21D7 Protein, a Nuclear Antigen Associated with Cell Division, Is a Component of the 26S Proteasome

“…Although these data may reflect an incomplete separation of the enzymatic complexes, another explanation is more likely. The free forms of the two main subcomplexes of the 26S proteasome, the 20S proteasome and the regulatory complex, have similar sedimentation coefficients (Tanahashi et al, 1993;Hoffman and Rechsteiner, 1994;Peters et al, 1994). Therefore, fractions of 20S proteasomes must contain free regulatory complexes recognized by the antibody against the 26S proteasome.…”

“…The 26s proteasome is a particle of approximately 2000 kD, formed by a 20s core catalytic complex and two large, polar, regulatory complexes (DeMartino and Slaughter, 1993;Peters et al, 1993Peters et al, , 1994Tanahashi et al, 1993). The 20s catalytic complex (or 20s proteasome) is an ATPindependent protease consisting of 15 to 20 subunits subdivided into two families, a-type and P-type (Lupas et al, 1994).…”

Yeast counterparts of subunits S5a and p58 (S3) of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1.

“…(Kanayama et al, 1992;Tanahashi et al, 1993). (C) Immunoblot analysis of the rat PA700 regulatory subunit complex with anti-Sun2p antibodies and anti-p58 peptide antibody.…”

Removal of proteasomes from the nucleus and their accumulation in apoptotic blebs during programmed cell death

“…In its 26S form it is the central protease of the ubiquitin-dependent pathway of protein degradation and has a highly conserved structure from yeast to man [12,13]. The proteasome is known to degrade a large number of key regulatory proteins [14], but its role in apoptosis is as yet unknown.…”