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452 a.a.
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439 a.a.
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13 a.a.
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Yeast mitochondrial processing peptidase beta-e73q mutant complexed with cytochromE C oxidase iv signal peptide
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Structure:
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Mitochondrial processing peptidase alpha subunit. Chain: a, c, e, g. Synonym: alpha-mpp. Engineered: yes. Mitochondrial processing peptidase beta subunit. Chain: b, d, f, h. Synonym: beta-mpp. Engineered: yes. Mutation: yes.
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Source:
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Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the 24 residue peptide of cytochromE C oxidase polypeptide iv was synthesized using standard solid-phase fmoc synthesis methodology
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Biol. unit:
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Trimer (from
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Resolution:
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2.70Å
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R-factor:
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0.229
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R-free:
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0.264
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Authors:
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A.B.Taylor,B.S.Smith,S.Kitada,K.Kojima,H.Miyaura,Z.Otwinowski,A.Ito, J.Deisenhofer
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Key ref:
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A.B.Taylor
et al.
(2001).
Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences.
Structure,
9,
615-625.
PubMed id:
DOI:
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Date:
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21-Dec-00
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Release date:
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11-Jul-01
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PROCHECK
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Headers
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References
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P11914
(MPPA_YEAST) -
Mitochondrial-processing peptidase subunit alpha from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
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Seq:
Struc:
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482 a.a.
452 a.a.*
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Enzyme class:
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Chains B, D, F, H:
E.C.3.4.24.64
- mitochondrial processing peptidase.
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Reaction:
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Release of N-terminal transit peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2.
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Cofactor:
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Zn(2+)
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DOI no:
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Structure
9:615-625
(2001)
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PubMed id:
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Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences.
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A.B.Taylor,
B.S.Smith,
S.Kitada,
K.Kojima,
H.Miyaura,
Z.Otwinowski,
A.Ito,
J.Deisenhofer.
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ABSTRACT
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BACKGROUND: Mitochondrial processing peptidase (MPP) is a metalloendopeptidase
that cleaves the N-terminal signal sequences of nuclear-encoded proteins
targeted for transport from the cytosol to the mitochondria. Mitochondrial
signal sequences vary in length and sequence, but each is cleaved at a single
specific site by MPP. The cleavage sites typically contain an arginine at
position -2 (in the N-terminal portion) from the scissile peptide bond in
addition to other distal basic residues, and an aromatic residue at position +1.
Mitochondrial import machinery recognizes amphiphilic helical conformations in
signal sequences. However, it is unclear how MPP specifically recognizes diverse
presequence substrates. RESULTS: The crystal structures of recombinant yeast MPP
and a cleavage-deficient mutant of MPP complexed with synthetic signal peptides
have been determined. MPP is a heterodimer; its alpha and beta subunits are
homologous to the core II and core I proteins, respectively, of the
ubiquinol-cytochrome c oxidoreductase complex. Crystal structures of two
different synthetic substrate peptides cocrystallized with the mutant MPP each
show the peptide bound in an extended conformation at the active site.
Recognition sites for the arginine at position -2 and the +1 aromatic residue
are observed. CONCLUSIONS: MPP bound two mitochondrial import presequence
peptides in extended conformations in a large polar cavity. The presequence
conformations differ from the amphiphilic helical conformation recognized by
mitochondrial import components. Our findings suggest that the presequences
adopt context-dependent conformations through mitochondrial import and
processing, helical for recognition by mitochondrial import machinery and
extended for cleavage by the main processing component.
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Selected figure(s)
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Figure 2.
Figure 2. The Central Cavity of MPP(a) Electrostatic
surface representation of MPP contoured at ±15 kcal calculated
by GRASP [58]. Positive charge is shown as blue and negative
charge as red. The flexible loop (residues a284-a301) is
circled.(b) A cutaway view of the surface representation of MPP
revealing the electrostatic potential of the central cavity
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2001,
9,
615-625)
copyright 2001.
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Figure was
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Y.Lu,
and
F.Liao
(2011).
Interferon-stimulated gene ISG12b2 is localized to the inner mitochondrial membrane and mediates virus-induced cell death.
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Cell Death Differ,
18,
925-936.
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A.M.Shiflett,
and
P.J.Johnson
(2010).
Mitochondrion-related organelles in eukaryotic protists.
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Annu Rev Microbiol,
64,
409-429.
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J.Thomas,
J.Fishovitz,
and
I.Lee
(2010).
Utilization of positional isotope exchange experiments to evaluate reversibility of ATP hydrolysis catalyzed by Escherichia coli Lon protease.
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Biochem Cell Biol,
88,
119-128.
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O.Schmidt,
N.Pfanner,
and
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(2010).
Mitochondrial protein import: from proteomics to functional mechanisms.
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Nat Rev Mol Cell Biol,
11,
655-667.
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Q.Guo,
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Y.Bian,
A.B.Schilling,
and
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(2010).
Molecular basis for the recognition and cleavages of IGF-II, TGF-alpha, and amylin by human insulin-degrading enzyme.
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J Mol Biol,
395,
430-443.
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PDB codes:
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Y.Yang,
B.P.Hubbard,
D.A.Sinclair,
and
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(2010).
Characterization of murine SIRT3 transcript variants and corresponding protein products.
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J Cell Biochem,
111,
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A.Chacinska,
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D.Milenkovic,
T.Lithgow,
and
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(2009).
Importing mitochondrial proteins: machineries and mechanisms.
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Cell,
138,
628-644.
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A.E.Aleshin,
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J.A.Tainer,
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and
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(2009).
Crystal and solution structures of a prokaryotic M16B peptidase: an open and shut case.
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Structure,
17,
1465-1475.
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PDB code:
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A.Parcellier,
L.A.Tintignac,
E.Zhuravleva,
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and
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(2009).
The Carboxy-Terminal Modulator Protein (CTMP) regulates mitochondrial dynamics.
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PLoS ONE,
4,
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A.Sickmann,
N.Pfanner,
and
C.Meisinger
(2009).
Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability.
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Cell,
139,
428-439.
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E.Malito,
R.E.Hulse,
and
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(2008).
Amyloid beta-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin.
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Cell Mol Life Sci,
65,
2574-2585.
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M.J.Page,
and
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Evolution of peptidase diversity.
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J Biol Chem,
283,
30010-30014.
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and
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(2008).
Assembly of the Iron-binding Protein Frataxin in Saccharomyces cerevisiae Responds to Dynamic Changes in Mitochondrial Iron Influx and Stress Level.
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J Biol Chem,
283,
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T.M.Embley,
J.Janata,
and
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(2008).
Reductive evolution of the mitochondrial processing peptidases of the unicellular parasites trichomonas vaginalis and giardia intestinalis.
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PLoS Pathog,
4,
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J.Strassner,
and
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(2008).
Cloning, expression and characterization of insulin-degrading enzyme from tomato (Solanum lycopersicum).
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Biol Chem,
389,
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A.Mukhopadhyay,
C.S.Yang,
B.Wei,
and
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(2007).
Precursor Protein Is Readily Degraded in Mitochondrial Matrix Space if the Leader Is Not Processed by Mitochondrial Processing Peptidase.
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J Biol Chem,
282,
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C.V.Galmozzi,
M.J.Fernández-Avila,
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and
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The ammonium-inactivated cyanobacterial glutamine synthetase I is reactivated in vivo by a mechanism involving proteolytic removal of its inactivating factors.
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and
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(2007).
Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE.
|
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J Biol Chem,
282,
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PDB codes:
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M.J.Baker,
A.E.Frazier,
J.M.Gulbis,
and
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(2007).
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I.Y.Gluzman,
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and
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(2007).
A role for falcilysin in transit peptide degradation in the Plasmodium falciparum apicoplast.
|
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Mol Microbiol,
63,
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M.T.Brown,
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F.Bastida-Corcuera,
M.G.Delgadillo-Correa,
A.G.McArthur,
and
P.J.Johnson
(2007).
A functionally divergent hydrogenosomal peptidase with protomitochondrial ancestry.
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64,
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O.Emanuelsson,
S.Brunak,
G.von Heijne,
and
H.Nielsen
(2007).
Locating proteins in the cell using TargetP, SignalP and related tools.
|
| |
Nat Protoc,
2,
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S.Kitada,
T.Uchiyama,
T.Funatsu,
Y.Kitada,
T.Ogishima,
and
A.Ito
(2007).
A protein from a parasitic microorganism, Rickettsia prowazekii, can cleave the signal sequences of proteins targeting mitochondria.
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J Bacteriol,
189,
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K.Yuksek,
R.Patel,
and
M.L.Summers
(2006).
Identification of Nostoc punctiforme akinete-expressed genes using differential display.
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Mol Microbiol,
61,
748-757.
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K.A.Johnson,
S.Bhushan,
A.Ståhl,
B.M.Hallberg,
A.Frohn,
E.Glaser,
and
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(2006).
The closed structure of presequence protease PreP forms a unique 10,000 Angstroms3 chamber for proteolysis.
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EMBO J,
25,
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PDB code:
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K.M.Honeychurch,
C.M.Byrd,
and
D.E.Hruby
(2006).
Mutational analysis of the potential catalytic residues of the VV G1L metalloproteinase.
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Virol J,
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(2006).
Regulation of mitochondrial morphology through proteolytic cleavage of OPA1.
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EMBO J,
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N.Pfanner,
and
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(2006).
The Tim21 binding domain connects the preprotein translocases of both mitochondrial membranes.
|
| |
EMBO Rep,
7,
1233-1238.
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PDB code:
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Y.Shen,
A.Joachimiak,
M.R.Rosner,
and
W.J.Tang
(2006).
Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism.
|
| |
Nature,
443,
870-874.
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PDB codes:
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C.G.Wilson,
T.Kajander,
and
L.Regan
(2005).
The crystal structure of NlpI. A prokaryotic tetratricopeptide repeat protein with a globular fold.
|
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FEBS J,
272,
166-179.
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PDB code:
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G.Ondrovicová,
T.Liu,
K.Singh,
B.Tian,
H.Li,
O.Gakh,
D.Perecko,
J.Janata,
Z.Granot,
J.Orly,
E.Kutejová,
and
C.K.Suzuki
(2005).
Cleavage site selection within a folded substrate by the ATP-dependent lon protease.
|
| |
J Biol Chem,
280,
25103-25110.
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H.Otera,
S.Ohsakaya,
Z.Nagaura,
N.Ishihara,
and
K.Mihara
(2005).
Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space.
|
| |
EMBO J,
24,
1375-1386.
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S.Wongtangtintharn,
H.Oku,
H.Iwasaki,
M.Inafuku,
T.Toda,
and
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(2005).
Incorporation of branched-chain fatty acid into cellular lipids and caspase-independent apoptosis in human breast cancer cell line, SKBR-3.
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Lipids Health Dis,
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N.Wiedemann,
A.E.Frazier,
and
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(2004).
The protein import machinery of mitochondria.
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J Biol Chem,
279,
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K.Brandner,
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T.S.Heard,
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P.K.Hammen,
and
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Location of the actual signal in the negatively charged leader sequence involved in the import into the mitochondrial matrix space.
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and
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| |
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PDB codes:
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N.R.Stanley,
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S.Richter,
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| |
J Biol Chem,
277,
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|
| |
Plant J,
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|
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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.
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Links
