The mitochondrial processing peptidase: function and specificity.
Targeting signals of mitochondrial precursors are cleaved in the matrix during or after import by the mitochondrial processing peptidase (MPP). This enzyme consists of two nonidentical alpha- and beta-subunits each of molecular weight of about 50 kDa. In mammals and fungi, MPP is soluble in the matrix, whereas in plants the enzyme is part of the cytochrome bc1 complex. MPP is a metalloendopeptidase which has been classified as a member of the pitrilysin family on the basis of the HXXEHX76E zinc-binding motif present in beta-MPP. Both subunits of MPP are required for processing activity. The alpha-subunit of MPP, which probably recognizes a three-dimensional motif adopted by the presequence, presents the presequence to beta-MPP, which carries the catalytic active site. MPP acts as an endoprotease on chemically synthesized peptides corresponding to mitochondrial presequences. Matrix-targeting signals and MPP cleavage signals seem to be distinct, although the two signals may overlap within a given presequence. The structural element helix-turn-helix, that cleavable presequences adopt in a membrane mimetic environment, may be required for processing but is not sufficient for proteolysis. Binding of the presequence by alpha-MPP tolerates a high degree of mutations of the presequence. alpha-MPP may present a degenerated cleavage site motif to beta-MPP in an accessible conformation for processing. The conformation of mitochondrial presequences bound to MPP remains largely unknown.
Luciano
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Laboratoire d'Ingéniérie des Systèmes Macromoléculaires, CNRS, Marseille, France.
Géli
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D007700:Kinetics; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D011487:Protein Conformation; D013379:Substrate Specificity; D015032:Zinc / Q000378:metabolism; D000096122:Mitochondrial Processing Peptidase
D008666:Metalloendopeptidases; D008667:Metalloproteins; D015032:Zinc; D000096122:Mitochondrial Processing Peptidase