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PDBsum entry 1hr7
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences.
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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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Ref.
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Structure, 2001,
9,
615-625.
[DOI no: ]
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PubMed id
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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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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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