PDBsum entry 1ksf

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Hydrolase, ligand binding protein PDB id
Jmol PyMol
Protein chain
714 a.a. *
PGE ×2
ADP ×2
IPA ×5
_MG ×2
Waters ×242
* Residue conservation analysis
PDB id:
Name: Hydrolase, ligand binding protein
Title: Crystal structure of clpa, an hsp100 chaperone and regulator of clpap protease: structural basis of differences in function of the two aaa+ atpase domains
Structure: Atp-dependent clp protease atp-binding subunit clpa. Chain: x. Synonym: endopeptidase clp atp-binding. Atp-binding component of serine protease. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
2.60Å     R-factor:   0.221     R-free:   0.304
Authors: F.Guo,M.R.Maurizi,L.Esser,D.Xia
Key ref:
F.Guo et al. (2002). Crystal structure of ClpA, an Hsp100 chaperone and regulator of ClpAP protease. J Biol Chem, 277, 46743-46752. PubMed id: 12205096 DOI: 10.1074/jbc.M207796200
12-Jan-02     Release date:   27-Sep-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P0ABH9  (CLPA_ECOLI) -  ATP-dependent Clp protease ATP-binding subunit ClpA
758 a.a.
714 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytosol   1 term 
  Biological process     response to oxidative stress   4 terms 
  Biochemical function     nucleotide binding     5 terms  


DOI no: 10.1074/jbc.M207796200 J Biol Chem 277:46743-46752 (2002)
PubMed id: 12205096  
Crystal structure of ClpA, an Hsp100 chaperone and regulator of ClpAP protease.
F.Guo, M.R.Maurizi, L.Esser, D.Xia.
Escherichia coli ClpA, an Hsp100/Clp chaperone and an integral component of the ATP-dependent ClpAP protease, participates in regulatory protein degradation and the dissolution and degradation of protein aggregates. The crystal structure of the ClpA subunit reveals an N-terminal domain with pseudo-twofold symmetry and two AAA(+) modules (D1 and D2) each consisting of a large and a small sub-domain with ADP bound in the sub-domain junction. The N-terminal domain interacts with the D1 domain in a manner similar to adaptor-binding domains of other AAA(+) proteins. D1 and D2 are connected head-to-tail consistent with a cooperative and vectorial translocation of protein substrates. In a planar hexamer model of ClpA, built by assembling ClpA D1 and D2 into homohexameric rings of known structures of AAA(+) modules, the differences in D1-D1 and D2-D2 interfaces correlate with their respective contributions to hexamer stability and ATPase activity.
  Selected figure(s)  
Figure 5.
Fig. 5. Hexameric model of ClpA. Electrostatic potential surface of the modeled planar ClpA hexagon as rendered in GRASP, with negative potential in red, positive in blue, and neutral in white. a, the hexagonal ring is viewed along the 6-fold axis with the D1 domains facing out. The hexagon has a crenated edge and maximum diameter of 170 Å. The larger crenations are made by the six N-domains, which are attached to the outer edge of the D1 domains; the smaller crenations are formed by extensions of the D2-small domains. b, the D2 side is facing out, showing the wide opening of the central cavity (red) and residues forming part of the ClpP loop (yellow). c, side view of the modeled ClpA hexagonal ring. The height is about 87 Å. The six subunits are shown in different colors. D1 and D2 from the same ClpA subunit are tilted with respect to the ring axis and make little contact with each other. Each domain makes extensive contacts with both D1 and D2 of a neighboring subunit. d, cross section through the center and parallel to the 6-fold axis of the modeled ClpA hexagonal ring. The surface of the central cavity is colored to show the three negatively charged belts (red) and the hydrophobic surfaces surrounding the channels (gray). The borders of the cavity are outlined in black. The two constrictions and the two compartments are as labeled. The positions for the three remaining ClpP loop are indicated in yellow.
Figure 6.
Fig. 6. A hypothetical model describing transitions of ClpA subunits in solution to form a spiral in crystal in the presence of ADP and to assemble into a planar hexamer in solution in the presence of ATP. ClpA subunits are postulated to undergo an open and a closed conformation by rotating D2 with respect to D1 via the hinge between two domains.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 46743-46752) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22562135 S.E.Glynn, A.R.Nager, T.A.Baker, and R.T.Sauer (2012).
Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine.
  Nat Struct Mol Biol, 19, 616-622.  
21266546 A.Kravats, M.Jayasinghe, and G.Stan (2011).
Unfolding and translocation pathway of substrate protein controlled by structure in repetitive allosteric cycles of the ClpY ATPase.
  Proc Natl Acad Sci U S A, 108, 2234-2239.  
21362118 C.Nashiro, A.Kashiwagi, T.Matsuzaki, S.Tamura, and Y.Fujiki (2011).
Recruiting Mechanism of the AAA Peroxins, Pex1p and Pex6p, to Pex26p on the Peroxisomal Membrane.
  Traffic, 12, 774-788.  
21368759 F.Wang, Z.Mei, Y.Qi, C.Yan, Q.Hu, J.Wang, and Y.Shi (2011).
Structure and mechanism of the hexameric MecA-ClpC molecular machine.
  Nature, 471, 331-335.
PDB codes: 2y1q 2y1r 3pxg 3pxi
22056769 M.Stotz, O.Mueller-Cajar, S.Ciniawsky, P.Wendler, F.U.Hartl, A.Bracher, and M.Hayer-Hartl (2011).
Structure of green-type Rubisco activase from tobacco.
  Nat Struct Mol Biol, 18, 1366-1370.
PDB codes: 3t15 3zw6
20851345 D.H.Li, Y.S.Chung, M.Gloyd, E.Joseph, R.Ghirlando, G.D.Wright, Y.Q.Cheng, M.R.Maurizi, A.Guarné, and J.Ortega (2010).
Acyldepsipeptide antibiotics induce the formation of a structured axial channel in ClpP: A model for the ClpX/ClpA-bound state of ClpP.
  Chem Biol, 17, 959-969.
PDB code: 3mt6
20462489 G.Effantin, T.Ishikawa, G.M.De Donatis, M.R.Maurizi, and A.C.Steven (2010).
Local and global mobility in the ClpA AAA+ chaperone detected by cryo-electron microscopy: functional connotations.
  Structure, 18, 553-562.  
19714768 S.Zietkiewicz, M.J.Slusarz, R.Slusarz, K.Liberek, and S.Rodziewicz-Motowidło (2010).
Conformational stability of the full-atom hexameric model of the ClpB chaperone from Escherichia coli.
  Biopolymers, 93, 47-60.  
19768774 V.Grimminger-Marquardt, and H.A.Lashuel (2010).
Structure and function of the molecular chaperone Hsp104 from yeast.
  Biopolymers, 93, 252-276.  
20512113 W.K.Tang, D.Li, C.C.Li, L.Esser, R.Dai, L.Guo, and D.Xia (2010).
A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants.
  EMBO J, 29, 2217-2229.
PDB codes: 3hu1 3hu2 3hu3
19361434 D.J.Kojetin, P.D.McLaughlin, R.J.Thompson, D.Dubnau, P.Prepiak, M.Rance, and J.Cavanagh (2009).
Structural and motional contributions of the Bacillus subtilis ClpC N-domain to adaptor protein interactions.
  J Mol Biol, 387, 639-652.
PDB code: 2k77
19362814 F.Striebel, W.Kress, and E.Weber-Ban (2009).
Controlled destruction: AAA+ ATPases in protein degradation from bacteria to eukaryotes.
  Curr Opin Struct Biol, 19, 209-217.  
19131969 G.Bönemann, A.Pietrosiuk, A.Diemand, H.Zentgraf, and A.Mogk (2009).
Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion.
  EMBO J, 28, 315-325.  
19451643 G.Román-Hernández, R.A.Grant, R.T.Sauer, and T.A.Baker (2009).
Molecular basis of substrate selection by the N-end rule adaptor protein ClpS.
  Proc Natl Acad Sci U S A, 106, 8888-8893.
PDB codes: 3g19 3g1b 3gq0 3gq1 3gw1
19008106 S.M.Doyle, and S.Wickner (2009).
Hsp104 and ClpB: protein disaggregating machines.
  Trends Biochem Sci, 34, 40-48.  
18682217 J.Bohon, L.D.Jennings, C.M.Phillips, S.Licht, and M.R.Chance (2008).
Synchrotron protein footprinting supports substrate translocation by ClpA via ATP-induced movements of the D2 loop.
  Structure, 16, 1157-1165.  
18466635 J.Snider, G.Thibault, and W.A.Houry (2008).
The AAA+ superfamily of functionally diverse proteins.
  Genome Biol, 9, 216.  
18995838 K.H.Wang, G.Roman-Hernandez, R.A.Grant, R.T.Sauer, and T.A.Baker (2008).
The molecular basis of N-end rule recognition.
  Mol Cell, 32, 406-414.
PDB code: 3dnj
18816064 L.D.Jennings, J.Bohon, M.R.Chance, and S.Licht (2008).
The ClpP N-terminus coordinates substrate access with protease active site reactivity.
  Biochemistry, 47, 11031-11040.  
18550799 L.Zhu, J.O.Wrabl, A.P.Hayashi, L.S.Rose, and P.J.Thomas (2008).
The torsin-family AAA+ protein OOC-5 contains a critical disulfide adjacent to Sensor-II that couples redox state to nucleotide binding.
  Mol Biol Cell, 19, 3599-3612.  
18929572 M.D.Gonciarz, F.G.Whitby, D.M.Eckert, C.Kieffer, A.Heroux, W.I.Sundquist, and C.P.Hill (2008).
Biochemical and structural studies of yeast Vps4 oligomerization.
  J Mol Biol, 384, 878-895.
PDB codes: 3eie 3eih
19013274 M.L.Mott, J.P.Erzberger, M.M.Coons, and J.M.Berger (2008).
Structural synergy and molecular crosstalk between bacterial helicase loaders and replication initiators.
  Cell, 135, 623-634.
PDB codes: 3ec2 3ecc
18755692 R.Lum, M.Niggemann, and J.R.Glover (2008).
Peptide and protein binding in the axial channel of Hsp104. Insights into the mechanism of protein unfolding.
  J Biol Chem, 283, 30139-30150.  
19000607 S.Sugimoto, Abdullah-Al-Mahin, and K.Sonomoto (2008).
Molecular chaperones in lactic acid bacteria: physiological consequences and biochemical properties.
  J Biosci Bioeng, 106, 324-336.  
18280501 Z.Yu, M.D.Gonciarz, W.I.Sundquist, C.P.Hill, and G.J.Jensen (2008).
Cryo-EM structure of dodecameric Vps4p and its 2:1 complex with Vta1p.
  J Mol Biol, 377, 364-377.  
17803938 D.M.Smith, S.C.Chang, S.Park, D.Finley, Y.Cheng, and A.L.Goldberg (2007).
Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry.
  Mol Cell, 27, 731-744.  
18160044 P.Wendler, J.Shorter, C.Plisson, A.G.Cashikar, S.Lindquist, and H.R.Saibil (2007).
Atypical AAA+ subunit packing creates an expanded cavity for disaggregation by the protein-remodeling factor Hsp104.
  Cell, 131, 1366-1377.  
17244533 S.Lee, J.M.Choi, and F.T.Tsai (2007).
Visualizing the ATPase cycle in a protein disaggregating machine: structural basis for substrate binding by ClpB.
  Mol Cell, 25, 261-271.  
17545305 S.M.Doyle, J.R.Hoskins, and S.Wickner (2007).
Collaboration between the ClpB AAA+ remodeling protein and the DnaK chaperone system.
  Proc Natl Acad Sci U S A, 104, 11138-11144.  
16810315 G.Thibault, Y.Tsitrin, T.Davidson, A.Gribun, and W.A.Houry (2006).
Large nucleotide-dependent movement of the N-terminal domain of the ClpX chaperone.
  EMBO J, 25, 3367-3376.  
16525504 J.Kirstein, T.Schlothauer, D.A.Dougan, H.Lilie, G.Tischendorf, A.Mogk, B.Bukau, and K.Turgay (2006).
Adaptor protein controlled oligomerization activates the AAA+ protein ClpC.
  EMBO J, 25, 1481-1491.  
16829961 J.P.Erzberger, M.L.Mott, and J.M.Berger (2006).
Structural basis for ATP-dependent DnaA assembly and replication-origin remodeling.
  Nat Struct Mol Biol, 13, 676-683.
PDB code: 2hcb
16879409 M.Zolkiewski (2006).
A camel passes through the eye of a needle: protein unfolding activity of Clp ATPases.
  Mol Microbiol, 61, 1094-1100.  
16483314 T.Okuno, K.Yamanaka, and T.Ogura (2006).
An AAA protease FtsH can initiate proteolysis from internal sites of a model substrate, apo-flavodoxin.
  Genes Cells, 11, 261-268.  
16877706 T.V.Rotanova, I.Botos, E.E.Melnikov, F.Rasulova, A.Gustchina, M.R.Maurizi, and A.Wlodawer (2006).
Slicing a protease: structural features of the ATP-dependent Lon proteases gleaned from investigations of isolated domains.
  Protein Sci, 15, 1815-1828.  
16046622 B.M.Burton, and T.A.Baker (2005).
Remodeling protein complexes: insights from the AAA+ unfoldase ClpX and Mu transposase.
  Protein Sci, 14, 1945-1954.  
15989952 G.L.Hersch, R.E.Burton, D.N.Bolon, T.A.Baker, and R.T.Sauer (2005).
Asymmetric interactions of ATP with the AAA+ ClpX6 unfoldase: allosteric control of a protein machine.
  Cell, 121, 1017-1027.  
15989953 J.Hinnerwisch, W.A.Fenton, K.J.Furtak, G.W.Farr, and A.L.Horwich (2005).
Loops in the central channel of ClpA chaperone mediate protein binding, unfolding, and translocation.
  Cell, 121, 1029-1041.  
14738756 A.Mogk, and B.Bukau (2004).
Molecular chaperones: structure of a protein disaggregase.
  Curr Biol, 14, R78-R80.  
14990998 C.M.Pickart, and R.E.Cohen (2004).
Proteasomes and their kin: proteases in the machine age.
  Nat Rev Mol Cell Biol, 5, 177-187.  
15208691 C.Schlieker, J.Weibezahn, H.Patzelt, P.Tessarz, C.Strub, K.Zeth, A.Erbse, J.Schneider-Mergener, J.W.Chin, P.G.Schultz, B.Bukau, and A.Mogk (2004).
Substrate recognition by the AAA+ chaperone ClpB.
  Nat Struct Mol Biol, 11, 607-615.  
14988733 I.Dreveny, H.Kondo, K.Uchiyama, A.Shaw, X.Zhang, and P.S.Freemont (2004).
Structural basis of the interaction between the AAA ATPase p97/VCP and its adaptor protein p47.
  EMBO J, 23, 1030-1039.
PDB code: 1s3s
14728719 J.Weibezahn, B.Bukau, and A.Mogk (2004).
Unscrambling an egg: protein disaggregation by AAA+ proteins.
  Microb Cell Fact, 3, 1.  
15550247 J.Weibezahn, P.Tessarz, C.Schlieker, R.Zahn, Z.Maglica, S.Lee, H.Zentgraf, E.U.Weber-Ban, D.A.Dougan, F.T.Tsai, A.Mogk, and B.Bukau (2004).
Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB.
  Cell, 119, 653-665.  
14962378 M.R.Maurizi, and D.Xia (2004).
Protein binding and disruption by Clp/Hsp100 chaperones.
  Structure, 12, 175-183.  
15031730 P.Laksanalamai, T.A.Whitehead, and F.T.Robb (2004).
Minimal protein-folding systems in hyperthermophilic archaea.
  Nat Rev Microbiol, 2, 315-324.  
15064753 S.A.Joshi, G.L.Hersch, T.A.Baker, and R.T.Sauer (2004).
Communication between ClpX and ClpP during substrate processing and degradation.
  Nat Struct Mol Biol, 11, 404-411.  
15606774 T.V.Rotanova, E.E.Melnikov, A.G.Khalatova, O.V.Makhovskaya, I.Botos, A.Wlodawer, and A.Gustchina (2004).
Classification of ATP-dependent proteases Lon and comparison of the active sites of their proteolytic domains.
  Eur J Biochem, 271, 4865-4871.  
12949490 B.DeLaBarre, and A.T.Brunger (2003).
Complete structure of p97/valosin-containing protein reveals communication between nucleotide domains.
  Nat Struct Biol, 10, 856-863.
PDB code: 1oz4
12925799 D.Y.Kim, C.A.Wu, D.R.Kim, S.C.Ha, Y.H.Han, and K.K.Kim (2003).
Purification, crystallization and preliminary X-ray studies of ClpX from Helicobacter pylori.
  Acta Crystallogr D Biol Crystallogr, 59, 1642-1644.  
12887894 H.K.Song, and M.J.Eck (2003).
Structural basis of degradation signal recognition by SspB, a specificity-enhancing factor for the ClpXP proteolytic machine.
  Mol Cell, 12, 75-86.
PDB codes: 1ox8 1ox9
12950913 R.Hengge, and B.Bukau (2003).
Proteolysis in prokaryotes: protein quality control and regulatory principles.
  Mol Microbiol, 49, 1451-1462.  
14570582 S.Gottesman (2003).
Proteolysis in bacterial regulatory circuits.
  Annu Rev Cell Dev Biol, 19, 565-587.  
14640692 S.Kedzierska, V.Akoev, M.E.Barnett, and M.Zolkiewski (2003).
Structure and function of the middle domain of ClpB from Escherichia coli.
  Biochemistry, 42, 14242-14248.  
14567920 S.Lee, M.E.Sowa, Y.H.Watanabe, P.B.Sigler, W.Chiu, M.Yoshida, and F.T.Tsai (2003).
The structure of ClpB: a molecular chaperone that rescues proteins from an aggregated state.
  Cell, 115, 229-240.
PDB code: 1qvr
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.