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PDBsum entry 2guz

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protein ligands Protein-protein interface(s) links
Chaperone, protein transport PDB id
2guz
Jmol
Contents
Protein chains
(+ 2 more) 71 a.a. *
(+ 2 more) 65 a.a. *
Ligands
FLC ×4
Waters ×921
* Residue conservation analysis
PDB id:
2guz
Name: Chaperone, protein transport
Title: Structure of the tim14-tim16 complex of the mitochondrial protein import motor
Structure: Mitochondrial import inner membrane translocase subunit tim14. Chain: a, c, e, g, i, k, m, o. Fragment: j-domain. Synonym: presequence translocated-associated motor subunit pam18. Engineered: yes. Mitochondrial import inner membrane translocase subunit tim16.
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: pam18, tim14. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: pam16, tim16. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.208     R-free:   0.253
Authors: D.Mokranjac,G.Bourenkov,K.Hell,W.Neupert,M.Groll
Key ref:
D.Mokranjac et al. (2006). Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor. EMBO J, 25, 4675-4685. PubMed id: 16977310 DOI: 10.1038/sj.emboj.7601334
Date:
02-May-06     Release date:   03-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q07914  (TIM14_YEAST) -  Mitochondrial import inner membrane translocase subunit TIM14
Seq:
Struc:
168 a.a.
71 a.a.*
Protein chains
Pfam   ArchSchema ?
P42949  (TIM16_YEAST) -  Mitochondrial import inner membrane translocase subunit TIM16
Seq:
Struc:
149 a.a.
65 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrial inner membrane presequence translocase complex   1 term 
  Biological process     protein import into mitochondrial matrix   1 term 

 

 
DOI no: 10.1038/sj.emboj.7601334 EMBO J 25:4675-4685 (2006)
PubMed id: 16977310  
 
 
Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor.
D.Mokranjac, G.Bourenkov, K.Hell, W.Neupert, M.Groll.
 
  ABSTRACT  
 
The import motor of the mitochondrial translocase of the inner membrane (TIM23) mediates the ATP-dependent translocation of preproteins into the mitochondrial matrix by cycles of binding to and release from mtHsp70. An essential step of this process is the stimulation of the ATPase activity of mtHsp70 performed by the J cochaperone Tim14. Tim14 forms a complex with the J-like protein Tim16. The crystal structure of this complex shows that the conserved domains of the two proteins have virtually identical folds but completely different surfaces enabling them to perform different functions. The Tim14-Tim16 dimer reveals a previously undescribed arrangement of J and J-like domains. Mutations that destroy the complex between Tim14 and Tim16 are lethal demonstrating that complex formation is an essential requirement for the viability of cells. We further demonstrate tight regulation of the cochaperone activity of Tim14 by Tim16. The first crystal structure of a J domain in complex with a regulatory protein provides new insights into the function of the mitochondrial TIM23 translocase and the Hsp70 chaperone system in general.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Topology and charge patterns of Tim14 and Tim16. (A) Ribbon presentations of the J domain of Tim14 (left panel) and the J-like domain of Tim16 (central panel). For comparison, the J domain of DnaJ from E. coli is included (right panel). Helices I–III are indicated. HPD motifs in the J domains are presented as balls-and-sticks models and colored in yellow. Corresponding DKE motif in Tim16 is colored in gray. As compared to the J domain of DnaJ, Tim14 and Tim16 lack helix IV. (B) Superposition of the J and J-like domains of Tim14, Tim16 and DnaJ. (C) Surface representations of Tim14, Tim16 and DnaJ. Ribbon presentations of the same orientation are shown as insets. The domains are rotated clockwise by 80° relative to the representations in (A) to bring helix II to the front. Surface colors indicate positive (intense blue) and negative electrostatic potentials (intense red) with the scale bar giving the actual potentials in kT/e. Lys and Arg residues of Tim14 contributing to the positive surface charge distribution are indicated.
Figure 6.
Figure 6 Evolutionary conservation of Tim14 and Tim16. Sequence alignment of Tim14 (A) and Tim16 (B) with their homologues. Identical residues are shown as white letters on black background and similar residues are shaded in gray. The characteristic helices of the J domain fold are indicated below the alignments. The HPD motif is shown in yellow. Predicted transmembrane domain (TM) of Tim14 is underlined. Red/blue pentagons—Tim14/Tim16 residues forming the hydrophobic cores of the J/J-like domains; Yellow circles—Tim14 residues which form the positively charged surface for interaction with mtHsp70; green squares/diamonds—residues involved in polar/hydrophobic interactions between Tim14 and Tim16. The parts of Tim14 and Tim16, which were crystallized, are boxed.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 4675-4685) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21390322 P.L.Jedelský, P.Doležal, P.Rada, J.Pyrih, O.Smíd, I.Hrdý, M.Sedinová, M.Marcinčiková, L.Voleman, A.J.Perry, N.C.Beltrán, T.Lithgow, and J.Tachezy (2011).
The minimal proteome in the reduced mitochondrion of the parasitic protist Giardia intestinalis.
  PLoS One, 6, e17285.  
21514823 P.T.Jubinsky, M.K.Short, M.Ghanem, and B.C.Das (2011).
Design, synthesis, and biological activity of novel Magmas inhibitors.
  Bioorg Med Chem Lett, 21, 3479-3482.  
21112411 P.Yu-Wai-Man, P.G.Griffiths, and P.F.Chinnery (2011).
Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies.
  Prog Retin Eye Res, 30, 81.  
20053669 D.Sinha, N.Joshi, B.Chittoor, P.Samji, and P.D'Silva (2010).
Role of Magmas in protein transport and human mitochondria biogenesis.
  Hum Mol Genet, 19, 1248-1262.  
20385092 K.Mapa, M.Sikor, V.Kudryavtsev, K.Waegemann, S.Kalinin, C.A.Seidel, W.Neupert, D.C.Lamb, and D.Mokranjac (2010).
The conformational dynamics of the mitochondrial Hsp70 chaperone.
  Mol Cell, 38, 89.  
20084418 K.Prymula, K.Sałapa, and I.Roterman (2010).
"Fuzzy oil drop" model applied to individual small proteins built of 70 amino acids.
  J Mol Model, 16, 1269-1282.  
20729931 O.Schmidt, N.Pfanner, and C.Meisinger (2010).
Mitochondrial protein import: from proteomics to functional mechanisms.
  Nat Rev Mol Cell Biol, 11, 655-667.  
19703392 A.Chacinska, C.M.Koehler, D.Milenkovic, T.Lithgow, and N.Pfanner (2009).
Importing mitochondrial proteins: machineries and mechanisms.
  Cell, 138, 628-644.  
19036727 D.Becker, M.Krayl, A.Strub, Y.Li, M.P.Mayer, and W.Voos (2009).
Impaired Interdomain Communication in Mitochondrial Hsp70 Results in the Loss of Inward-directed Translocation Force.
  J Biol Chem, 284, 2934-2946.  
19519518 J.Li, X.Qian, and B.Sha (2009).
Heat shock protein 40: structural studies and their functional implications.
  Protein Pept Lett, 16, 606-612.  
19564938 S.Elsner, D.Simian, O.Iosefson, M.Marom, and A.Azem (2009).
The Mitochondrial Protein Translocation Motor: Structural Conservation between the Human and Yeast Tim14/Pam18-Tim16/Pam16 co-Chaperones.
  Int J Mol Sci, 10, 2041-2053.  
18400944 D.P.Hutu, B.Guiard, A.Chacinska, D.Becker, N.Pfanner, P.Rehling, and M.van der Laan (2008).
Mitochondrial protein import motor: differential role of Tim44 in the recruitment of Pam17 and J-complex to the presequence translocase.
  Mol Biol Cell, 19, 2642-2649.  
18418384 D.Popov-Celeketić, K.Mapa, W.Neupert, and D.Mokranjac (2008).
Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria.
  EMBO J, 27, 1469-1480.  
18174896 N.Bolender, A.Sickmann, R.Wagner, C.Meisinger, and N.Pfanner (2008).
Multiple pathways for sorting mitochondrial precursor proteins.
  EMBO Rep, 9, 42-49.  
18003975 P.R.D'Silva, B.Schilke, M.Hayashi, and E.A.Craig (2008).
Interaction of the j-protein heterodimer pam18/pam16 of the mitochondrial import motor with the translocon of the inner membrane.
  Mol Biol Cell, 19, 424-432.  
17696772 D.Milenkovic, J.Müller, D.Stojanovski, N.Pfanner, and A.Chacinska (2007).
Diverse mechanisms and machineries for import of mitochondrial proteins.
  Biol Chem, 388, 891-897.  
17452317 D.Mokranjac, A.Berg, A.Adam, W.Neupert, and K.Hell (2007).
Association of the Tim14.Tim16 subcomplex with the TIM23 translocase is crucial for function of the mitochondrial protein import motor.
  J Biol Chem, 282, 18037-18045.  
18070913 N.Wiedemann, M.van der Laan, D.P.Hutu, P.Rehling, and N.Pfanner (2007).
Sorting switch of mitochondrial presequence translocase involves coupling of motor module to respiratory chain.
  J Cell Biol, 179, 1115-1122.  
17919282 P.Genevaux, C.Georgopoulos, and W.L.Kelley (2007).
The Hsp70 chaperone machines of Escherichia coli: a paradigm for the repartition of chaperone functions.
  Mol Microbiol, 66, 840-857.  
17263664 W.Neupert, and J.M.Herrmann (2007).
Translocation of proteins into mitochondria.
  Annu Rev Biochem, 76, 723-749.  
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.