DECIPHERING THE FLAGELLUM ATTACHMENT ZONE (FAZ) IN TRYPANOSOMA BRUCEI

Abstract

C2 domains are ubiquitously present in eukaryotic cells, mediating protein interactions with lipid membranes. Many C2 domain families can be traced back to the last eukaryotic common ancestor (LECA) species, suggesting early emergence and functional specialization of this domain. Most structural analyses have focused on the Ca2+-dependent interaction PKC-C2 domains interaction with lipids. Here in this project, we describe the structural and cellular function of the C2 domain of CC2D, a protein conserved among the early-branching kinetoplastid parasites. In T. brucei, it is associated with both the basal bodies and the flagellum attachment zone (FAZ), through which the flagellum is attached to the cell body. The CC2D-C2 domain interacted with lipids in a Ca2+ -independent manner, involving five arginine residues located between strands b6 and b8. Our results also revealed a previously unappreciated role of CC2D in membrane lipid organization and flagellar protein targeting, supporting a function of the FAZ in linking cytoskeleton and membrane organization.