ABSTRACT
BILBO1 was the first characterized component of the flagellar pocket collar (FPC) in trypanosomes. The N-terminal domain (NTD) of BILBO1 plays an essential role in T. brucei FPC biogenesis and is thus vital for the parasite’s survival. Here we report a 1.7-Å resolution crystal structure of TbBILBO1-NTD, which revealed a conserved horseshoe-like hydrophobic pocket formed by an unusually long loop. Mutagenesis studies suggested that another FPC protein, FPC4, interacts with TbBILBO1 via specific binding to this pocket. Overall, we have determined the exact binding site of TbFPC4 on TbBILBO1-NTD, which may provide a basis for rational drug design in the future.
Background BILBO1 is the core component of the flagellar pocket collar (FPC) in trypanosomes and recruits other FPC proteins including FPC4 to form this essential cytoskeleton-associated structure in kinetoplastids.
Results We determined a high-resolution crystal structure of the N-terminal domain of T. brucei BILBO1, which revealed a characteristic horseshoe-like surface pocket for specific binding of T. brucei FPC4.
Conclusion The C-terminal loop of the TbBILBO1 N-terminal domain adopts an unusual circular conformation to provide a unique contact site for TbFPC4 binding.
Significance The crystal structure together with mutagenesis studies reveals for the first time how two FPC proteins interact with each other.