Reductive evolution of the mitochondrial processing peptidases of the unicellular parasites trichomonas vaginalis and giardia intestinalis.
Mitochondrial processing peptidases are heterodimeric enzymes (alpha/betaMPP) that play an essential role in mitochondrial biogenesis by recognizing and cleaving the targeting presequences of nuclear-encoded mitochondrial proteins. The two subunits are paralogues that probably evolved by duplication of a gene for a monomeric metallopeptidase from the endosymbiotic ancestor of mitochondria. Here, we characterize the MPP-like proteins from two important human parasites that contain highly reduced versions of mitochondria, the mitosomes of Giardia intestinalis and the hydrogenosomes of Trichomonas vaginalis. Our biochemical characterization of recombinant proteins showed that, contrary to a recent report, the Trichomonas processing peptidase functions efficiently as an alpha/beta heterodimer. By contrast, and so far uniquely among eukaryotes, the Giardia processing peptidase functions as a monomer comprising a single betaMPP-like catalytic subunit. The structure and surface charge distribution of the Giardia processing peptidase predicted from a 3-D protein model appear to have co-evolved with the properties of Giardia mitosomal targeting sequences, which, unlike classic mitochondrial targeting signals, are typically short and impoverished in positively charged residues. The majority of hydrogenosomal presequences resemble those of mitosomes, but longer, positively charged mitochondrial-type presequences were also identified, consistent with the retention of the Trichomonas alphaMPP-like subunit. Our computational and experimental/functional analyses reveal that the divergent processing peptidases of Giardia mitosomes and Trichomonas hydrogenosomes evolved from the same ancestral heterodimeric alpha/betaMPP metallopeptidase as did the classic mitochondrial enzyme. The unique monomeric structure of the Giardia enzyme, and the co-evolving properties of the Giardia enzyme and substrate, provide a compelling example of the power of reductive evolution to shape parasite biology.
Smíd
Ondrej
O
Department of Parasitology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Matusková
Anna
A
Harris
Simon R
SR
Kucera
Tomás
T
Novotný
Marián
M
Horváthová
Lenka
L
Hrdý
Ivan
I
Kutejová
Eva
E
Hirt
Robert P
RP
Embley
T Martin
TM
Janata
Jirí
J
Tachezy
Jan
J
D000595:Amino Acid Sequence; D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D019143:Evolution, Molecular; D018628:Gene Dosage; D016829:Giardia lamblia / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D005998:Glycine / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D006859:Hydrogen / Q000378:metabolism; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D015388:Organelles / Q000378:metabolism; D010802:Phylogeny; D055232:Proline-Rich Protein Domains / Q000235:genetics / Q000502:physiology; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics; D021381:Protein Transport; D014246:Trichomonas vaginalis / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D000096122:Mitochondrial Processing Peptidase
D005998:Glycine; D006859:Hydrogen; D008666:Metalloendopeptidases; D021122:Protein Subunits; D000096122:Mitochondrial Processing Peptidase