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Proteasome Subunit Specific Antibodies


Biomol offers a large selection of antibodies to proteasome subunits.

The Proteasome

The proteasome is a very large protein complex, located in the nucleus and the cytoplasm. The principal function of the proteasome is to degrade unneeded or damaged proteins by proteolysis. The degradation process by the proteasome proteases yields peptides of about seven to eight amino acids length. Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ubiquitin ligases. Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin molecules. The result is a polyubiquitin chain that is bound by the proteasome, allowing it to degrade the tagged protein.

Proteasome Structure

The structure of a proteasome is a cylindrical complex containing a core of four stacked rings around a central pore (called 20S proteasome). Each ring is composed of seven individual proteins. The inner two rings are made of seven β subunits that contain the six protease active sites. These sites are located on the interior surface of the rings, so that the target protein must enter the central pore before it is degraded. The outer two rings each contain seven α subunits whose function is to maintain a gate through which proteins enter the barrel. These α subunits are controlled by binding to a regulatory cap structure (19S proteasome) that recognize polyubiquitin tags attached to protein substrates and initiate the degradation process. The overall system of ubiquitination and proteasomal degradation is known as the ubiquitin-proteasome system.

The proteasome subcomponents are often referred to by their Svedberg sedimentation coefficient (denoted S). The most common form of the proteasome is known as the 26S proteasome, which is about 2000 kilodaltons (kDa) in molecular mass and contains one 20S core particle structure and two 19S regulatory caps. The core is hollow and provides an enclosed cavity in which proteins are degraded; openings at the two ends of the core allow the target protein to enter. Each end of the core particle associates with a 19S regulatory subunit that contains multiple ATPase active sites and ubiquitin binding sites; it is this structure that recognizes polyubiquitinated proteins and transfers them to the catalytic core. An alternative form of regulatory subunit called the 11S regulatory particle can associate with the core in essentially the same manner as the 19S particle; the 11S regulatory particle may play a role in degradation of foreign peptides such as those produced after infection by a virus.

20S core particle

20S particles consist of four stacked heptameric ring structures that are themselves composed of two different types of subunits; α subunits are structural in nature, whereas β subunits are predominantly catalytic. The outer two rings in the stack consist of seven α subunits each, which serve as docking domains for the regulatory particles and the alpha subunits N-termini form a gate that blocks unregulated access of substrates to the interior cavity. The inner two rings each consist of seven β subunits and contain the protease active sites that perform the proteolysis reactions. The size of the proteasome is about 15 nm by 11.5 nm. The interior chamber is at most 5.3 nm wide, though the entrance can be as narrow as 1.3 nm, suggesting that substrate proteins must be at least partially unfolded to enter.

The β1 (PSMB1), β7 (PSMB7, "β2" called by Baumeister et al.), and β5 (PSMB5) subunits are catalytic; although they share a common mechanism, they have three distinct substrate specificities considered chymotrypsin-like, trypsin-like, and peptidyl-glutamyl peptide-hydrolyzing (PHGH). Alternative β forms denoted β9 (PSMB9, "β1i" called by Baumeister et al.), β10 (PSMB10, "β2i" by Baumeister et al.), and β8 (PSMB8, "β5i" according to Baumeister et al.) can be expressed in hematopoietic cells in response to exposure to pro-inflammatory signals such as cytokines, in particular, interferon gamma. The proteasome assembled with these alternative subunits is known as the immunoproteasome, whose substrate specificity is altered relative to the normal proteasome.

The nomenclature is somewhat confusing, we stick to the "official" nomenclature as found on www.uniprot.org, but alternative names can be found in the listings below, too. The antibodies are named by the official name, but ordered by the names given by Baumeister et al.

Antibodies to 20S α-type subunits
P60900 α1, iota, Pros27, p27k, C7, Prs2, Y8, Scl1: α6 PSMA6 Antibodies
P25787 α2, C3, Pre8, Prs4, Y7: α2 PSMA2 Antibodies
P25789 α3, C9, Pre9, Prs5, Y13: α4 PSMA4 Antibodies
O14818 α4, C6, XAPC-7, Pre6: α7 PSMA7 Antibodies
P28066 α5, zeta, Pup2, Doa5: α5 PSMA5 Antibodies
P25786 α6, C2, nu, Pros30, p30k, Pre5: α1 PSMA1 Antibodies
P25788 α7, C8, Pre10, Prs1, C1, Prc1: α3 PSMA3 Antibodies

Antibodies to 20S β-type subunits
P28072 β1, Y, delta, Lmp9, Pre3: β6 PSMB6 Antibodies
P28065 β1i, Lmp2, Ring12: β9 PSMB9 Antibodies
Q99436 β2, Z, Lmp19, MC14, Pup1: β7 PSMB7 Antibodies
P40306 β2i, MECL-1, Lmp10: β10 PSMB10 Antibodies
P49720 β3, C10, theta, Pup3: β3 PSMB3 Antibodies
P49721 β4, C7, Pre1, C11: β2 PSMB2 Antibodies
P28074 β5, X, epsilon, Lmp17,MB1, Pre2, Doa3, Prg1: β5 PSMB5 Antibodies
P28062 β5i, Lmp7, Ring10, Y2, C13: β8 PSMB8 Antibodies
P20618 β6, C5, gamma, pre7, Prs3,C5, Pts1: β1 PSMB1 Antibodies
P28070 β7, N3, beta, Pros26, Pre4: β4 PSMB4 Antibodies

19S regulatory particle

The 19S particle consists of 19 individual proteins and is divisible into two subassemblies, a 10-protein base that binds directly to the α ring of the 20S core particle, and a 9-protein lid where polyubiquitin is bound. The association of the 19S and 20S particles requires the binding of ATP to the 19S ATPase subunits, and ATP hydrolysis is required for the assembled complex to degrade folded and ubiquitinated proteins.

Antibodies to 19S (PA700) regulator ATPase subunits
P35998 Rpt1, S7, p48, Mss1, Yta3, Cim5: subunit 7 PSMC2 Antibodies
P62191 Rpt2, S4, p56, Yhs4, Yta5, Mts2: subunit 4 PSMC1 Antibodies
P43686 Rpt3, S6b, S6, p48, Tbp7, Yta2, Ynt1, MS73: subunit 6b PSMC4 Antibodies
P62333 Rpt4, S10b, p42, Sug2, Pcs1, Crl13, CADp44: subunit 10b PSMC6 Antibodies
P17980 Rpt5, S6a, S6, p50, Tbp1, Yta1: subunit 6a PSMC3 Antibodies
P62195 Rpt6, S8, p45, Trip1, Sug1, Cim3, Crl3, Tby1, Tbp10, m56: subunit 8 PSMC5 Antibodies

Antibodies to 19S (PA700) regulator ATPase subunits
Q13200 Rpn1, S2, p97, Trap2, Nas1, Hrd2, Ppd1, Mts4: subunit 2 PSMD2 Antibodies
Q99460 Rpn2, S1, p112, Sen3: subunit 1 PSMD1 Antibodies
O43242 Rpn3, S3, p58, Sun2: subunit 3 PSMD3 Antibodies
O00232 Rpn5, p55, Nas5: subunit 12 PSMD12 Antibodies
O00231 Rpn6, S9, p44.5: subunit 11 PSMD11 Antibodies
Q15008 Rpn7, S10a, p44, HUMORF07: subunit 6 PSMD6 Antibodies
P51665 Rpn8, S12, p40, Mov-34h, Mas3: subunit 7 PSMD7 Antibodies
Q9UNM6 Rpn9, S11, p40.5, Les1, Nas7: subunit 13 PSMD13 Antibodies
P55036 Rpn10, S5a, p54, ASF1, Sun1, Mcb1, Mbp1: subunit 4 PSMD4 Antibodies
O00487 Rpn11, S13, Poh1, Mpr1, Pad1h: subunit 14 PSMD14 Antibodies
P48556 Rpn12, S14, p31, Nin1, Mts3: subunit 8 PSMD8 Antibodies
Q16401 S5b, p50.5 subunit 5 PSMD5 Antibodies
O00233 S15, p27-L: subunit 9 PSMD9 Antibodies
O75832 Gankyrin, p28, Nas6: subunit 10 PSMD10 Antibodies

11S regulatory particle

20S proteasomes can also associate with a second type of regulatory particle, the 11S regulatory particle, a heptameric structure that does not contain any ATPases and can promote the degradation of short peptides, but not of complete proteins. This structure is also known as PA28 or REG. The expression of the 11S particle is induced by interferon gamma and is responsible, in conjunction with the immunoproteasome α subunits, for the generation of peptides that bind to the major histocompatibility complex.

Antibodies to 11S Activator
Q06323 11Sα, PA28α, REGα: subunit 1 PSME1 Antibodies
Q9UL46 11Sβ, PA28β, REGβ: subunit 2 PSME2 Antibodies
P61289 11Sγ, PA28γ, REGγ: subunit 3 PSME3 Antibodies

See also: COP9 Signalosome: Antibodies to the CSN Complex


Proteasome Pathway Map
W. Baumeister et al. The proteasome paradigm of a self-compartimentalizing protease. Cell 1998 92 367
W. Dubiel et al. Subunits of the regulatory complex of the 26S protease. Mol. Biol. Reports 1995 21 27
W. Dubiel et al. Purification of an 11S regulator of the multicatlytic protease. J. Biol. Chem. 1992 267 22369
C. P. Ma et al. Identification, purification, and characeterization of a protein activator (PA28) of the proteasome (macropain). J. Biol. Chem. 1992 267 10515
C. Realini et al. Characterization of the recombinant REGAα, REGβ, and REGγ proteasome activators. J. Biol. Chem. 1997 272 25483

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