Structure of the TbBILBO1 Protein N-terminal domain from Trypanosoma brucei reveals an essential requirement for a Conserved surface patch

Abstract

Background: TbBILBO1 is the only known component of the flagellar pocket collar, a cytoskeletal structure in the parasite Trypanosoma brucei. Results: The TbBILBO1 N-terminal domain has a ubiquitin-like fold with a conserved surface patch; overexpression of constructs with a mutagenized patch is lethal. Conclusion: The conserved surface patch is essential for TbBILBO1 function. Significance: The surface patch is a potential therapeutic target. 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.© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.