ClpS is an essential component of the N-end rule pathway in Escherichia coli

Erbse, Annette H.; Schmidt, Ronny; Bornemann, Thomas; Schneider‐Mergener, Jens; Mogk, Axel; Zahn, Regina; Dougan, David A.; Bukau, Bernd

doi:10.1038/nature04412

Cited by 203 publications

(294 citation statements)

References 18 publications

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“…The reason for this conclusion is that any one of the latter four residues, if made N-terminal, would be directly recognized as a Nd p residue by the ClpS-ClpAP targeting͞proteolytic complex (Fig. 1B) (31). Because the degradation of Asp-␤gal and Glu-␤gal, the substrates of V. vulnificus Bpt, was not affected by the absence of V. vulnificus Aat, and because a converse omission of V. vulnificus Bpt from E. coli expressing V. vulnificus Aat did not perturb the degradation of Aat substrates Arg-␤gal and Lys-␤gal ( Fig.…”

Section: Bpt Transferase Has a Hybrid Recognition͞conjugation Specifimentioning

confidence: 99%

“…Asp-␤gal and Glu-␤gal are normally long-lived in E. coli, because N-terminal Asp and Glu are stabilizing residues in this prokaryote, in that they are not recognized by either the Aat L͞F K,R -transferase or the rest of the E. coli N-end rule pathway (25,26,31). Previous work (13,17,36) has shown that the steady-state level of an X-␤gal reporter is a sensitive measure of its metabolic stability.…”

Section: Bpt Transferase Has a Hybrid Recognition͞conjugation Specifimentioning

confidence: 99%

“…ClpS, a 12-kDa adaptor protein specific for ClpAP, is an essential component of the E. coli N-end rule pathway, where it functions as the N-recognin (Fig. 1B) (31).…”

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confidence: 99%

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Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen

Graciet

Hu²,

Piatkov³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

115

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The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Primary destabilizing N-terminal residues (Nd p ) are recognized directly by the targeting machinery. The recognition of secondary destabilizing N-terminal residues (Nd s ) is preceded by conjugation of an Nd p residue to Nd s of a polypeptide substrate. In eukaryotes, ATE1 -encoded arginyl-transferases (R D,E,C* -transferases) conjugate Arg (R), an Nd p residue, to Nd s residues Asp (D), Glu (E), or oxidized Cys residue (C*). Ubiquitin ligases recognize the N-terminal Arg of a substrate and target the (ubiquitylated) substrate to the proteasome. In prokaryotes such as Escherichia coli , Nd p residues Leu (L) or Phe (F) are conjugated, by the aat -encoded Leu/Phe-transferase (L/F K,R -transferase), to N-terminal Arg or Lys, which are Nd s in prokaryotes but Nd p in eukaryotes. In prokaryotes, substrates bearing the Nd p residues Leu, Phe, Trp, or Tyr are degraded by the proteasome-like ClpAP protease. Despite enzymological similarities between eukaryotic R D,E,C* -transferases and prokaryotic L/F K,R -transferases, there is no significant sequelogy (sequence similarity) between them. We identified an aminoacyl-transferase, termed Bpt, in the human pathogen Vibrio vulnificus . Although it is a sequelog of eukaryotic R D,E,C* -transferases, this prokaryotic transferase exhibits a “hybrid” specificity, conjugating Nd p Leu to Nd s Asp or Glu. Another aminoacyl-transferase, termed ATEL1, of the eukaryotic pathogen Plasmodium falciparum , is a sequelog of prokaryotic L/F K,R -transferases (Aat), but has the specificity of eukaryotic R D,E,C* -transferases (ATE1). Phylogenetic analysis suggests that the substrate specificity of R-transferases arose by two distinct routes during the evolution of eukaryotes.

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Section: Bpt Transferase Has a Hybrid Recognition͞conjugation Specifimentioning

confidence: 99%

Section: Bpt Transferase Has a Hybrid Recognition͞conjugation Specifimentioning

confidence: 99%

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Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen

Graciet

Hu²,

Piatkov³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

115

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“…Some bacterial adapter proteins alter substrate preferences. For example, the ClpS adapter protein specifically inhibits the degradation of ssrA-tagged substrates by ClpAP but stimulates ClpAP to degrade aggregated proteins and possibly N-end rule substrates [76][77][78]. The use of adaptors allows for an additional level of regulation of degradation.…”

Section: Adapter Proteinsmentioning

confidence: 99%

Protein targeting to ATP-dependent proteases

Inobe

Matouschek

2008

Current Opinion in Structural Biology

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ATP-dependent proteases control diverse cellular processes by degrading specific regulatory proteins. Understanding how these regulatory proteins are targeted to ATP-dependent proteases is of central importance to understanding their biological role as regulators. Recent work has shown that protein substrates are specifically transferred to ATP-dependent proteases through different routes. These routes can function in parallel or independently. In all of these targeting mechanisms it can be useful to separate two steps: substrate binding to the protease and initiation of degradation.To be active, newly synthesized protein chains must fold into three-dimensional structures, but regulated unfolding is also critically important in some biological processes, such as protein degradation by ATP-dependent proteases and protein translocation across membranes [1]. Unfolding is required during degradation because the proteolytic sites of the ATP-dependent proteases are sequestered deep inside the proteases' structures and accessible only through narrow openings. Similarly, unfolding is required during several translocation processes because the protein import channels in some organelles are not wide enough for native proteins to fit through them. The mechanisms of unfolding in both types of processes are similar to each other but different from that of unfolding induced by heat or chemical denaturants. Here we discuss how the requirement for protein unfolding during degradation affects the way ATPdependent proteases select their substrates. ATP-dependent proteasesATP-dependent proteases degrade short-lived regulatory proteins and thereby control cellular processes such as signal transduction, cell cycle, and gene transcription. The proteases also clear misfolded and aggregated proteins from the cell and produce some of the peptides to be displayed at cell surface as part of adaptive immune response. In eukaryotes, these functions are performed mainly by the proteasome. In prokaryotes and the organelles of eukaryotes, the functions are fulfill by analogues of the proteasome, such as the ClpAP, ClpXP, HslUV, FtsH, and Lon proteases. Although ATP-dependent proteases show only relatively little sequence identity, they share a common architecture [2].The ATP-dependent proteases all form large multisubunit particles (Figure 1). In the simplest case, FtsH protease, the particle consists 6 copies of a 71 kDa subunit forming a complex of approximately 425 kDa, and in the most complex case, the proteasome, the particle consists of some 40 different subunits forming a complex of 2 MDa molecular weight [3,4]. The subunits are mostly arranged in six or seven subunit rings that stack on top of each other to

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“…37 Moreover, other AAAþ proteases interact with multiple types of peptide signals to identify the correct substrates. 7,[38][39][40][41][42][43][44][45] The AAAþ p97 protein also employs its N domain to interact with disparate sequences in a wide variety of adaptors. 46 The peptide-binding versatility exhibited by the ClpX N domain and SspB ensures that ClpXP can recognize many different substrates and adaptors in different ways but with high specificity.…”

Section: Discussionmentioning

confidence: 99%

Versatile modes of peptide recognition by the ClpX N domain mediate alternative adaptor‐binding specificities in different bacterial species

et al. 2010

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ClpXP, an AAA1 protease, plays key roles in protein-quality control and many regulatory processes in bacteria. The N-terminal domain of the ClpX component of ClpXP is involved in recognition of many protein substrates, either directly or by binding the SspB adaptor protein, which delivers specific classes of substrates for degradation. Despite very limited sequence homology between the E. coli and C. crescentus SspB orthologs, each of these adaptors can deliver substrates to the ClpXP enzyme from the other bacterial species. We show that the ClpX N domain recognizes different sequence determinants in the ClpX-binding (XB) peptides of C. crescentus SspBa and E. coli SspB. The C. crescentus XB determinants span 10 residues and involve interactions with multiple side chains, whereas the E. coli XB determinants span half as many residues with only a few important side chain contacts. These results demonstrate that the N domain of ClpX functions as a highly versatile platform for peptide recognition, allowing the emergence during evolution of alternative adaptor-binding specificities. Our results also reveal highly conserved residues in the XB peptides of both E. coli SspB and C. crescentus SspBa that play no detectable role in ClpX-binding or substrate delivery.

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ClpS is an essential component of the N-end rule pathway in Escherichia coli

Cited by 203 publications

References 18 publications

Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen

Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen

Protein targeting to ATP-dependent proteases

Versatile modes of peptide recognition by the ClpX N domain mediate alternative adaptor‐binding specificities in different bacterial species

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