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PROSITE documentation PDOC00668 [for PROSITE entry PS51476]

Proteasome beta-type subunit signature and profile





Description

The proteasome (or macropain) (EC 3.4.25.1) [1,2,3,4,5,6,7] is a multicatalytic proteinase complex that seems to be involved in an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. The core of this 2.5 MDa enzyme complex is formed by the 20S proteasome (core particle, CP), a barrel-shaped protease of about 700 KDa that associates with one or two 19S regulatory complexes. The 20S proteasome subunits can be classified, on the basis of sequence similarities, into two related families, α (see <PDOC00326>) and β. All archaea and eukaryotes have a 20S proteasome as well as some actinobacteria, but most bacteria have a simpler homologous structure heat shock locus v (HslV) or ClpQ. The HslV subunit has sequence similarity with the β-type subunits of the 20S proteasome.

The 20S proteasome is composed of four stacked heptameric rings. Narrow substrate entry channels are created by the two outer rings, which are each formed by seven α subunits. The two inner rings create an internal chamber that houses the proteolytic active sites responsible for protein cleavage; these rings are each formed by seven β subunits (see <PDOC00668>). 20S proteasome α subunits include highly conserved N-terminal extensions that are absent from β subunits. These N-termini form a gate that controls substrate passage through the central α-ring channel. Archaeal and bacterial 20S proteasomes usually have a single type of α subunit and β subunit, each present in 14 copies in each particle. Thus, these proteasomes have 14 active sites arrayed within their central chambers. In eukaryotes, seven distinct α-subunit paralogs form each heptameric outer ring and seven distinct β-subunit paralogs form each inner ring. Only three of the seven eukaryotic β subunits (β1, β2 and β5) retain an intact active site, so each eukaryotic 20S proteasome has six proteolytic active sites. The 20S proteasome is a threonine protease in which the active-site Thr residue is at the N-terminus of the β subunit. These subunits are activated following autocatalytic processing of an N-terminal propeptide. Propeptide autocleavage and substrate proteolysis utilize closely related mechanisms. The Thr residue is part of a conserved Thr-Lys-Asp catalytic triad, which functions similarly in both processes [8]. The ClpQ is a bacterial heat shock protein encoded by the heat shock locus V (hslV) and is regarded as a phylogenetic ancestor of the 20S proteasome. The homododecamer core consists of only two hexameric rings [7,9].

Some subunits that are known to belong to this family are listed below:

  • Vertebrate subunits C5, β, delta, epsilon, theta (C10-II), LMP2/RING12, C13 (LMP7/RING10), C7-I and MECL-1.
  • Yeast PRE1, PRE2 (PRG1), PRE3, PRE4, PRS3, PUP1 and PUP3.
  • Drosophila L(3)73AI.
  • Fission yeast pts1.
  • Thermoplasma acidophilum β-subunit. In this archaebacteria the proteasome is composed of only two different subunits.
  • Rhodococcus erythropolis 20S proteasome β subunit 1 (PrcB 1) and 2 (PrcB 2).
  • Escherichia coli ATP-dependent protease subunit HslV (EC=3.4.25.2).

Subunits that belong to the β-type group are proteins of from 190 to 290 amino acids that share a number of conserved sequence regions. The proteasome β-type subunit structure consists of a core of two antiparallel β sheets that is flanked by α helices on both sides (see <PDB:1PMA>) [10].

As a signature pattern for proteasome B-type subunits we selected the best conserved region, which is located in the N-terminal part of these proteins. The pattern is specific for the 20S-subtype and does not detect the HslV-subtype. We also have developed a profile which covers the whole conserved region of both subtypes.

Note:

These proteins belong to family T1 in the classification of peptidases [11,E2].

Last update:

May 2020 / Text revised.

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Technical section

PROSITE methods (with tools and information) covered by this documentation:

PROTEASOME_BETA_2, PS51476; Proteasome beta-type subunit profile  (MATRIX)

PROTEASOME_BETA_1, PS00854; Proteasome beta-type subunits signature  (PATTERN)


References

1AuthorsRivett A.J.
TitleProteasomes: multicatalytic proteinase complexes.
SourceBiochem. J. 291:1-10(1993).
PubMed ID7682410

2AuthorsRivett A.J.
TitleThe multicatalytic proteinase of mammalian cells.
SourceArch. Biochem. Biophys. 268:1-8(1989).
PubMed ID2643381

3AuthorsGoldberg A.L. Rock K.L.
TitleProteolysis, proteasomes and antigen presentation.
SourceNature 357:375-379(1992).
PubMed ID1317508
DOI10.1038/357375a0

4AuthorsWilk S.
TitleProteasomes. Multicatalytic proteinase complexes.
SourceEnzyme Protein 47:187-188(1993).
PubMed ID7697118

5AuthorsHilt W. Wolf D.H.
TitleProteasomes: destruction as a programme.
SourceTrends Biochem. Sci. 21:96-102(1996).
PubMed ID8882582

6AuthorsKwon Y.D. Nagy I. Adams P.D. Baumeister W. Jap B.K.
TitleCrystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly.
SourceJ. Mol. Biol. 335:233-245(2004).
PubMed ID14659753

7AuthorsBochtler M. Ditzel L. Groll M. Huber R.
TitleCrystal structure of heat shock locus V (HslV) from Escherichia coli.
SourceProc. Natl. Acad. Sci. U.S.A. 94:6070-6074(1997).
PubMed ID9177170

8AuthorsBudenholzer L. Cheng C.L. Li Y. Hochstrasser M.
TitleProteasome Structure and Assembly.
SourceJ. Mol. Biol. 429:3500-3524(2017).
PubMed ID28583440
DOI10.1016/j.jmb.2017.05.027

9AuthorsGille C. Goede A. Schloetelburg C. Preissner R. Kloetzel P.M. Goebel U.B. Frommel C.
TitleA comprehensive view on proteasomal sequences: implications for the evolution of the proteasome.
SourceJ. Mol. Biol. 326:1437-1448(2003).
PubMed ID12595256
DOI10.1016/s0022-2836(02)01470-5

10AuthorsLoewe J. Stock D. Jap B. Zwickl P. Baumeister W. Huber R. "Crystal structure of the 20S proteasome from the archaeon T.
Titleacidophilum at 3.4 A resolution.
SourceScience 268:533-539(1995).
PubMed ID7725097

11AuthorsRawlings N.D. Barrett A.J.
TitleFamilies of serine peptidases.
SourceMethods Enzymol. 244:19-61(1994).
PubMed ID7845208

E2Titlehttps://www.uniprot.org/docs/peptidas



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