Home LiteratureArticle Details
PMID: 15004005 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role of the processing pore of the ClpX AAA+ ATPase in the recognition and engagement of specific protein substrates.

Genes & development ·Vol. 18 ·No. 4 ·2004-02-15 ·Pages 369-74

Siddiqui SM, Sauer RT, Baker TA

Abstract

ClpX binds substrates bearing specific classes of peptide signals, denatures these proteins, and translocates them through a central pore into ClpP for degradation. ClpX with the V154F po e mutation is severely defective in binding substrates bearing C-motif 1 degradation signals and is also impaired in a subsequent step of substrate engagement. In contrast, this mutant efficiently processes substrates with other classes of recognition signals both in vitro and in vivo. These results demonstrate that the ClpX pore functions in the recognition and catalytic engagement of specific substrates, and that ClpX recognizes different substrate classes in at least two distinct fashions.

MeSH Terms
ATPases Associated with Diverse Cellular Activities Adenosine Triphosphatases/chemistry,genetics,metabolism Amino Acid Sequence Binding Sites Catalysis Endopeptidase Clp Escherichia coli Proteins Kinetics Molecular Chaperones Molecular Sequence Data Mutagenesis Peptide Fragments/chemistry Protein Transport Recombinant Proteins/chemistry,metabolism Restriction Mapping Substrate Specificity
Chemicals
Escherichia coli Proteins Molecular Chaperones Peptide Fragments Recombinant Proteins Endopeptidase Clp Adenosine Triphosphatases ClpX protein, E coli ATPases Associated with Diverse Cellular Activities
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Siddiqui Samia M
Massachusetts Institute of Technology, Department of Biology, Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA.
Sauer Robert T
Baker Tania A
References (27)
27 references, click to expand
  1. Conserved pore residues in the AAA protease FtsH are important for proteolysis and its coupling to ATP hydrolysis.
    J Biol Chem. 2003 Dec 12;278(50):50182-7 PMID: 14514680
  2. Proteolysis in prokaryotes: protein quality control and regulatory principles.
    Mol Microbiol. 2003 Sep;49(6):1451-62 PMID: 12950913
  3. The ClpX heat-shock protein of Escherichia coli, the ATP-dependent substrate specificity component of the ClpP-ClpX protease, is a novel molecular chaperone.
    EMBO J. 1995 May 1;14(9):1867-77 PMID: 7743994
  4. Disassembly of the Mu transposase tetramer by the ClpX chaperone.
    Genes Dev. 1995 Oct 1;9(19):2399-408 PMID: 7557391
  5. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA.
    Science. 1996 Feb 16;271(5251):990-3 PMID: 8584937
  6. ClpX protein of Escherichia coli activates bacteriophage Mu transposase in the strand transfer complex for initiation of Mu DNA synthesis.
    EMBO J. 1996 Feb 15;15(4):935-44 PMID: 8631314
  7. The structure of ClpP at 2.3 A resolution suggests a model for ATP-dependent proteolysis.
    Cell. 1997 Nov 14;91(4):447-56 PMID: 9390554
  8. PDZ-like domains mediate binding specificity in the Clp/Hsp100 family of chaperones and protease regulatory subunits.
    Cell. 1997 Dec 26;91(7):939-47 PMID: 9428517
  9. The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system.
    Genes Dev. 1998 May 1;12(9):1338-47 PMID: 9573050
  10. Regulation of endonuclease activity by proteolysis prevents breakage of unmodified bacterial chromosomes by type I restriction enzymes.
    Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9757-62 PMID: 10449767
  11. Global unfolding of a substrate protein by the Hsp100 chaperone ClpA.
    Nature. 1999 Sep 2;401(6748):90-3 PMID: 10485712
  12. Dynamics of substrate denaturation and translocation by the ClpXP degradation machine.
    Mol Cell. 2000 Apr;5(4):639-48 PMID: 10882100
  13. Unfolding and internalization of proteins by the ATP-dependent proteases ClpXP and ClpAP.
    Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8898-903 PMID: 10922052
  14. A specificity-enhancing factor for the ClpXP degradation machine.
    Science. 2000 Sep 29;289(5488):2354-6 PMID: 11009422
  15. Mutational studies on HslU and its docking mode with HslV.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14103-8 PMID: 11114186
  16. Visualization of substrate binding and translocation by the ATP-dependent protease, ClpXP.
    Mol Cell. 2000 Dec;6(6):1515-21 PMID: 11163224
  17. Molecular determinants of complex formation between Clp/Hsp100 ATPases and the ClpP peptidase.
    Nat Struct Biol. 2001 Mar;8(3):230-3 PMID: 11224567
  18. Effects of protein stability and structure on substrate processing by the ClpXP unfolding and degradation machine.
    EMBO J. 2001 Jun 15;20(12):3092-100 PMID: 11406586
  19. Crystal structures of the HslVU peptidase-ATPase complex reveal an ATP-dependent proteolysis mechanism.
    Structure. 2001 Feb 7;9(2):177-84 PMID: 11250202
  20. ATP-dependent proteases degrade their substrates by processively unraveling them from the degradation signal.
    Mol Cell. 2001 Mar;7(3):627-37 PMID: 11463387
  21. Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis.
    Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10584-9 PMID: 11535833
  22. Characterization of a specificity factor for an AAA+ ATPase: assembly of SspB dimers with ssrA-tagged proteins and the ClpX hexamer.
    Chem Biol. 2002 Nov;9(11):1237-45 PMID: 12445774
  23. C-terminal domain mutations in ClpX uncouple substrate binding from an engagement step required for unfolding.
    Mol Microbiol. 2003 Apr;48(1):67-76 PMID: 12657045
  24. Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals.
    Mol Cell. 2003 Mar;11(3):671-83 PMID: 12667450
  25. Mu transpososome architecture ensures that unfolding by ClpX or proteolysis by ClpXP remodels but does not destroy the complex.
    Chem Biol. 2003 May;10(5):463-72 PMID: 12770828
  26. Linkage between ATP consumption and mechanical unfolding during the protein processing reactions of an AAA+ degradation machine.
    Cell. 2003 Aug 22;114(4):511-20 PMID: 12941278
  27. Crystal structure of ClpX molecular chaperone from Helicobacter pylori.
    J Biol Chem. 2003 Dec 12;278(50):50664-70 PMID: 14514695
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
2004-02-15
Pages
369-74
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC359390
Subset
IM
Grants
NIAID NIH HHS · R01 AI016892 · United States
NIGMS NIH HHS · R01 GM049224 · United States
NIGMS NIH HHS · R01 GM049224-11 · United States
NIAID NIH HHS · AI-16892 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com