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Cited by 10Trypanosoma species research and implicationsMitochondrial Function and PathologyMicrotubule and mitosis dynamics

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Molecular characterization of the permanent outer-inner membrane contact site of the mitochondrial genome segregation complex in trypanosomes

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Stettler, Philip, Schimanski, Bernd, Aeschlimann, Salome, Schneider, André·2024·PLOS Pathogens
DOI 10.1371/journal.ppat.1012635PMC PMC11637284

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Abstract

The parasitic protozoan Trypanosoma brucei has a single unit mitochondrial genome linked to the basal body of the flagellum via the tripartite attachment complex (TAC). The TAC is crucial for mitochondrial genome segregation during cytokinesis. At the core of the TAC, the outer membrane protein TAC60 binds to the inner membrane protein p166, forming a permanent contact site between the two membranes. Although contact sites between mitochondrial membranes are common and serve various functions, their molecular architecture remains largely unknown. This study elucidates the interaction interface of the TAC60-p166 contact site. Using in silico , in vitro , and mutational in vivo analyses, we identified minimal binding segments between TAC60 and p166. The p166 binding site in TAC60 consists of a short kinked α-helix that interacts with the C-terminal α-helix of p166. Despite the presence of conserved charged residues in either protein, electrostatic interactions are not necessary for contact site formation. Instead, the TAC60-p166 interaction is driven by the hydrophobic effect, as converting conserved hydrophobic residues in either protein to hydrophilic amino acids disrupts the contact site.

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Metadata

Authors
Stettler, P., Schimanski, B., Aeschlimann, S., & Schneider, A.
Affiliations
University of Bern (CH)
Corresponding author
Schneider, André
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2024-12-02
Volume
20
Issue
12
Pages
e1012635
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1012635
PMC
PMC11637284
OpenAlex
W4404906214
Cited by
10
References
3
Citations by year
2026: 5 · 2025: 5
FWCI
3.03
Type
journal article
Language
en
Update notices
new_version (2024-12-12)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF 205200, NCCR, RNA & Disease, 205601)
Topics
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
Trypanosoma brucei, hydrophobic interactions, protein-protein interaction, cytokinesis, basal bodies, flagella
MeSH terms
Binding Sites, Mitochondria, Trypanosoma brucei brucei, Protozoan Proteins, Mitochondrial Proteins, Mitochondrial Membranes, Genome, Mitochondrial

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