title: Leishmania donovani HslV does not interact stably with HslU proteins.
abstract: Genes for HslVU-type peptidases are found in bacteria and in a few select Eukaryota, among those such important pathogens as Plasmodium spp. and Leishmania spp. In this study, we performed replacements of all three HslV/HslU gene homologues and found one of those, HslV, to be essential for Leishmania donovani viability. The Leishmania HslV gene can also partially relieve the thermosensitive phenotype of a combined HslVU/Lon/ClpXP knockout mutant of Escherichia coli, indicating a conserved function. However, we found that the role and function of the two Leishmania HslU genes has diverged since neither of those interacts stably with HslV. The latter forms a dodecameric complex by itself and shows a punctate distribution. We conclude that whilst the basic function of HslV may be conserved in Leishmania, its organisation and interaction with its canonical complex partner HslU is not. Nevertheless, given the absence of HslV from the proteome of mammals and its essential role in Leishmania viability, HslV is a promising target for intervention.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Chrobak
authors.forename: Sabine
authors.initials: S
authors.lastname: Förster
authors.forename: Sarah
authors.initials: S
authors.lastname: Meisel
authors.forename: Roxana
authors.initials: R
authors.lastname: Pfefferkorn
authors.forename: Frank
authors.initials: F
authors.lastname: Förster
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
mesh_terms: D004926:Escherichia coli / Q000235:genetics; D017353:Gene Deletion; D005816:Genetic Complementation Test; D007893:Leishmania donovani / Q000502:physiology*; D050296:Microbial Viability; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D010447:Peptide Hydrolases