title: Structure of the TbBILBO1 protein N-terminal domain from Trypanosoma brucei reveals an essential requirement for a conserved surface patch.
abstract: TbBILBO1 is the only known component of the flagellar pocket collar, a cytoskeletal barrier element found in trypanosomes. The N-terminal domain (NTD) of TbBILBO1 was found to be dispensable for targeting of the protein in vivo. However, overexpression of constructs lacking the NTD caused complete growth inhibition, implying an essential requirement for this domain. A high resolution structure of the NTD of TbBILBO1 showed that it forms a ubiquitin-like fold with a conserved surface patch. Mutagenesis of this patch recapitulated the phenotypic effects of deleting the entire domain and was found to cause cell death. The surface patch on the NTD of TbBILBO1 is therefore a potential drug target.
authors.affiliation: From the Max F. Perutz Laboratories, Medical University of Vienna, 1030 Vienna, Austria and.
authors.forename: Keni
authors.initials: K
authors.lastname: Vidilaseris
authors.forename: Brooke
authors.initials: B
authors.lastname: Morriswood
authors.forename: Georg
authors.initials: G
authors.lastname: Kontaxis
authors.forename: Gang
authors.initials: G
authors.lastname: Dong
mesh_terms: D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014346:Trypanosoma brucei brucei / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins
keywords: Cytoskeleton; Flagellar Pocket Collar; Infectious Diseases; Molecular Cell Biology; Nuclear Magnetic Resonance; Parasite; Protein Structure; Structural Biology; TbBILBO1; Trypanosoma brucei