{PDOC00668} {PS00854; PROTEASOME_BETA_1} {PS51476; PROTEASOME_BETA_2} {BEGIN} ****************************************************** * Proteasome beta-type subunit signature and profile * ****************************************************** The proteasome (or macropain) (EC 3.4.25.1) [1 to 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, alpha (see ) and beta. 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 beta-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 alpha 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 beta subunits (see ). 20S proteasome alpha subunits include highly conserved N-terminal extensions that are absent from beta subunits. These N-termini form a gate that controls substrate passage through the central alpha-ring channel. Archaeal and bacterial 20S proteasomes usually have a single type of alpha subunit and beta 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 alpha-subunit paralogs form each heptameric outer ring and seven distinct beta-subunit paralogs form each inner ring. Only three of the seven eukaryotic beta subunits (beta1, beta2 and beta5) 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 beta 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, beta, 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 beta-subunit. In this archaebacteria the proteasome is composed of only two different subunits. - Rhodococcus erythropolis 20S proteasome beta 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 beta-type group are proteins of from 190 to 290 amino acids that share a number of conserved sequence regions. The proteasome beta-type subunit structure consists of a core of two antiparallel beta sheets that is flanked by alpha helices on both sides (see ) [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. -Consensus pattern: [LIVMACFT]-[GSA]-[LIVMF]-x-[FYLVGAC]-x(2)-[GSACFYI]- [LIVMSTACF]-[LIVMSTAC]-[LIVMFSTAC]-[GACI]-[GSTACV]-[DES]- x(15,16)-[RK]-x(12,13)-G-x(2)-[GSTA]-D -Sequences known to belong to this class detected by the profile: ALL. 93 . -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: These proteins belong to family T1 in the classification of peptidases [11,E2]. -Last update: May 2020 / Text revised. [ 1] Rivett A.J. "Proteasomes: multicatalytic proteinase complexes." Biochem. J. 291:1-10(1993). PubMed=7682410 [ 2] Rivett A.J. "The multicatalytic proteinase of mammalian cells." Arch. Biochem. Biophys. 268:1-8(1989). PubMed=2643381 [ 3] Goldberg A.L., Rock K.L. "Proteolysis, proteasomes and antigen presentation." Nature 357:375-379(1992). PubMed=1317508; DOI=10.1038/357375a0 [ 4] Wilk S. "Proteasomes. Multicatalytic proteinase complexes." Enzyme Protein 47:187-188(1993). PubMed=7697118 [ 5] Hilt W., Wolf D.H. "Proteasomes: destruction as a programme." Trends Biochem. Sci. 21:96-102(1996). PubMed=8882582 [ 6] Kwon Y.D., Nagy I., Adams P.D., Baumeister W., Jap B.K. "Crystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly." J. Mol. Biol. 335:233-245(2004). PubMed=14659753 [ 7] Bochtler M., Ditzel L., Groll M., Huber R. "Crystal structure of heat shock locus V (HslV) from Escherichia coli." Proc. Natl. Acad. Sci. U.S.A. 94:6070-6074(1997). PubMed=9177170 [ 8] Budenholzer L., Cheng C.L., Li Y., Hochstrasser M. "Proteasome Structure and Assembly." J. Mol. Biol. 429:3500-3524(2017). PubMed=28583440; DOI=10.1016/j.jmb.2017.05.027 [ 9] Gille C., Goede A., Schloetelburg C., Preissner R., Kloetzel P.M., Goebel U.B., Frommel C. "A comprehensive view on proteasomal sequences: implications for the evolution of the proteasome." J. Mol. Biol. 326:1437-1448(2003). PubMed=12595256; DOI=10.1016/s0022-2836(02)01470-5 [10] Loewe J., Stock D., Jap B., Zwickl P., Baumeister W., Huber R. "Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution." Science 268:533-539(1995). PubMed=7725097 [11] Rawlings N.D., Barrett A.J. "Families of serine peptidases." Methods Enzymol. 244:19-61(1994). PubMed=7845208 [E2] https://www.uniprot.org/docs/peptidas -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}