title: A functionally divergent hydrogenosomal peptidase with protomitochondrial ancestry.
abstract: Matrix proteins of mitochondria, hydrogenosomes and mitosomes are typically targeted and translocated into their respective organelles using N-terminal presequences that are subsequently cleaved by a peptidase. Here we characterize a approximately 47 kDa metallopeptidase, from the hydrogenosome-bearing, unicellular eukaryote Trichomonas vaginalis, that contains the active site motif (HXXEHX(76)E) characteristic of the beta subunit of the mitochondrial processing peptidase (MPP) and localizes to hydrogenosomes. The purified recombinant protein, named hydrogenosomal processing peptidase (HPP), is capable of cleaving a hydrogenosomal presequence in vitro, in contrast to MPP which requires both an alpha and beta subunit for activity. T. vaginalis HPP forms an approximately 100 kDa homodimer in vitro and also exists in an approximately 100 kDa complex in vivo. Our phylogenetic analyses support a common origin for HPP and betaMPP and demonstrate that gene duplication gave rise to alphaMPP and betaMPP before the divergence of T. vaginalis and mitochondria-bearing lineages. These data, together with published analyses of MPPs and putative mitosomal processing peptidases, lead us to propose that the length of targeting presequences and the subunit composition of organellar processing peptidases evolved in concert. Specifically, longer mitochondrial presequences may have evolved to require an alpha/beta heterodimer for accurate cleavage, while shorter hydrogenosomal and mitosomal presequences did not.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 609 Charles E. Young Drive East, Los Angeles, CA 90095-1489, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Brown
authors.forename: Heather M H
authors.initials: HM
authors.lastname: Goldstone
authors.forename: Felix
authors.initials: F
authors.lastname: Bastida-Corcuera
authors.forename: Maria G
authors.initials: MG
authors.lastname: Delgadillo-Correa
authors.forename: Andrew G
authors.initials: AG
authors.lastname: McArthur
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Johnson
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D020440:Gene Duplication; D017125:Genes, Protozoan; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D014246:Trichomonas vaginalis / Q000201:enzymology / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D011498:Protein Precursors; D021122:Protein Subunits; D011994:Recombinant Proteins; D010450:Endopeptidases; D010447:Peptide Hydrolases