PDBsum entry 2cea

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Hydrolase PDB id
Protein chains
(+ 0 more) 407 a.a. *
ADP ×6
_MG ×6
_ZN ×6
Waters ×199
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Cell division protein ftsh
Structure: Cell division protein ftsh. Chain: a, b, c, d, e, f. Fragment: cytoplasmic domain, residues 147-610. Engineered: yes. Mutation: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: german collection of microorganisms (dsmz)
Biol. unit: Hexamer (from PDB file)
2.75Å     R-factor:   0.216     R-free:   0.262
Authors: C.Bieniossek,U.Baumann
Key ref:
C.Bieniossek et al. (2006). The molecular architecture of the metalloprotease FtsH. Proc Natl Acad Sci U S A, 103, 3066-3071. PubMed id: 16484367 DOI: 10.1073/pnas.0600031103
03-Feb-06     Release date:   09-Feb-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9WZ49  (FTSH_THEMA) -  ATP-dependent zinc metalloprotease FtsH
610 a.a.
407 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     membrane   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     nucleotide binding     4 terms  


DOI no: 10.1073/pnas.0600031103 Proc Natl Acad Sci U S A 103:3066-3071 (2006)
PubMed id: 16484367  
The molecular architecture of the metalloprotease FtsH.
C.Bieniossek, T.Schalch, M.Bumann, M.Meister, R.Meier, U.Baumann.
The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog causes a form of spastic paraplegia. FtsH plays a crucial role in quality control by degrading unneeded or damaged membrane proteins, but it also targets soluble signaling factors like sigma(32) and lambda-CII. We report here the crystal structure of a soluble FtsH construct that is functional in caseinolytic and ATPase assays. The molecular architecture of this hexameric molecule consists of two rings where the protease domains possess an all-helical fold and form a flat hexagon that is covered by a toroid built by the AAA domains. The active site of the protease classifies FtsH as an Asp-zincin, contrary to a previous report. The different symmetries of protease and AAA rings suggest a possible translocation mechanism of the target polypeptide chain into the interior of the molecule where the proteolytic sites are located.
  Selected figure(s)  
Figure 2.
Fig. 2. The hexameric structure of FtsH. (A) Top view approximately down the crystallographic twofold axis from the supposed membrane side onto the AAA ring. The colors denote the individual subunits. ADP and active site residues are shown as sticks (gray, carbons; blue, nitrogens; red, oxygens; cyan, phosphorous), and the Zn^2+ ions are shown as golden spheres. (B) Side view, the AAA ring is on the bottom, the protease ring on the top.
Figure 4.
Fig. 4. Surface representation. (A) Top view onto AAA ring. Phe-234 residues are colored in yellow and magenta, and Arg-318 is in orange. The orientation is the same as in Fig. 2A. ADP residues are shown as sticks. Subunits are shaded alternately light and dark. (B) Modeled ideal hexameric arrangement of the AAA domains. The protease ring is in the same orientation as in A and Fig. 2A.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23023677 R.M.Raju, A.L.Goldberg, and E.J.Rubin (2012).
Bacterial proteolytic complexes as therapeutic targets.
  Nat Rev Drug Discov, 11, 777-789.  
20154147 B.Gilquin, E.Taillebourg, N.Cherradi, A.Hubstenberger, O.Gay, N.Merle, N.Assard, M.O.Fauvarque, S.Tomohiro, O.Kuge, and J.Baudier (2010).
The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes.
  Mol Cell Biol, 30, 1984-1996.  
20130684 M.Esaki, and T.Ogura (2010).
ATP-bound form of the D1 AAA domain inhibits an essential function of Cdc48p/p97.
  Biochem Cell Biol, 88, 109-117.  
20834233 S.S.Cha, Y.J.An, C.R.Lee, H.S.Lee, Y.G.Kim, S.J.Kim, K.K.Kwon, G.M.De Donatis, J.H.Lee, M.R.Maurizi, and S.G.Kang (2010).
Crystal structure of Lon protease: molecular architecture of gated entry to a sequestered degradation chamber.
  EMBO J, 29, 3520-3530.
PDB code: 3k1j
20581825 T.Krojer, J.Sawa, R.Huber, and T.Clausen (2010).
HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues.
  Nat Struct Mol Biol, 17, 844-852.
PDB codes: 3mh4 3mh5 3mh6 3mh7
20666930 X.Liu, F.Yu, and S.Rodermel (2010).
Arabidopsis chloroplast FtsH, var2 and suppressors of var2 leaf variegation: a review.
  J Integr Plant Biol, 52, 750-761.  
19955424 C.Bieniossek, B.Niederhauser, and U.M.Baumann (2009).
The crystal structure of apo-FtsH reveals domain movements necessary for substrate unfolding and translocation.
  Proc Natl Acad Sci U S A, 106, 21579-21584.
PDB code: 3kds
19412571 E.D.Brenner, P.Feinberg, S.Runko, and G.M.Coruzzi (2009).
A mutation in the Proteosomal Regulatory Particle AAA-ATPase-3 in Arabidopsis impairs the light-specific hypocotyl elongation response elicited by a glutamate receptor agonist, BMAA.
  Plant Mol Biol, 70, 523-533.  
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.  
19748354 S.Augustin, F.Gerdes, S.Lee, F.T.Tsai, T.Langer, and T.Tatsuta (2009).
An intersubunit signaling network coordinates ATP hydrolysis by m-AAA proteases.
  Mol Cell, 35, 574-585.  
19914167 S.E.Glynn, A.Martin, A.R.Nager, T.A.Baker, and R.T.Sauer (2009).
Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine.
  Cell, 139, 744-756.
PDB codes: 3hte 3hws
19841671 T.Karlberg, S.van den Berg, M.Hammarström, J.Sagemark, I.Johansson, L.Holmberg-Schiavone, and H.Schüler (2009).
Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7.
  PLoS One, 4, e6975.
PDB code: 2qz4
19596908 W.B.Inwood, J.A.Hall, K.S.Kim, L.Demirkhanyan, D.Wemmer, H.Zgurskaya, and S.Kustu (2009).
Epistatic effects of the protease/chaperone HflB on some damaged forms of the Escherichia coli ammonium channel AmtB.
  Genetics, 183, 1327-1340.  
18931677 A.Martin, T.A.Baker, and R.T.Sauer (2008).
Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding.
  Nat Struct Mol Biol, 15, 1147-1151.  
18313382 A.Martin, T.A.Baker, and R.T.Sauer (2008).
Diverse pore loops of the AAA+ ClpX machine mediate unassisted and adaptor-dependent recognition of ssrA-tagged substrates.
  Mol Cell, 29, 441-450.  
18329872 E.J.Enemark, and L.Joshua-Tor (2008).
On helicases and other motor proteins.
  Curr Opin Struct Biol, 18, 243-257.  
18287278 I.Mochalkin, J.D.Knafels, and S.Lightle (2008).
Crystal structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor.
  Protein Sci, 17, 450-457.
PDB code: 2ves
18394159 J.C.Zweers, I.Barák, D.Becher, A.J.Driessen, M.Hecker, V.P.Kontinen, M.J.Saller, L.Vavrová, and J.M.van Dijl (2008).
Towards the development of Bacillus subtilis as a cell factory for membrane proteins and protein complexes.
  Microb Cell Fact, 7, 10.  
18421140 S.H.Kim, G.B.Kang, H.E.Song, S.J.Park, M.H.Bea, and S.H.Eom (2008).
Structural studies on Helicobacter pyloriATP-dependent protease, FtsH.
  J Synchrotron Radiat, 15, 208-210.
PDB codes: 2r62 2r65
18721134 S.Halder, S.Banerjee, and P.Parrack (2008).
Direct CIII-HflB interaction is responsible for the inhibition of the HflB (FtsH)-mediated proteolysis of Escherichia coli sigma(32) by lambdaCIII.
  FEBS J, 275, 4767-4772.  
17483203 C.Leidhold, and W.Voos (2007).
Chaperones and proteases--guardians of protein integrity in eukaryotic organelles.
  Ann N Y Acad Sci, 1113, 72-86.  
17261594 M.Graef, G.Seewald, and T.Langer (2007).
Substrate recognition by AAA+ ATPases: distinct substrate binding modes in ATP-dependent protease Yme1 of the mitochondrial intermembrane space.
  Mol Cell Biol, 27, 2476-2485.  
17101804 M.Koppen, M.D.Metodiev, G.Casari, E.I.Rugarli, and T.Langer (2007).
Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia.
  Mol Cell Biol, 27, 758-767.  
18023171 P.A.Tucker, and L.Sallai (2007).
The AAA+ superfamily--a myriad of motions.
  Curr Opin Struct Biol, 17, 641-652.  
17890311 S.Halder, A.B.Datta, and P.Parrack (2007).
Probing the antiprotease activity of lambdaCIII, an inhibitor of the Escherichia coli metalloprotease HflB (FtsH).
  J Bacteriol, 189, 8130-8138.  
17245427 T.Tatsuta, S.Augustin, M.Nolden, B.Friedrichs, and T.Langer (2007).
m-AAA protease-driven membrane dislocation allows intramembrane cleavage by rhomboid in mitochondria.
  EMBO J, 26, 325-335.  
17112720 P.R.Mittl, and M.G.Grütter (2006).
Opportunities for structure-based design of protease-directed drugs.
  Curr Opin Struct Biol, 16, 769-775.  
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 code is shown on the right.