p67: a cryptic lysosomal hydrolase in trypanosoma brucei?

Carolina M. Koeller, Terry K. Smith, Andrew M. Gulick, James D. Bangs

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


p67 is a type I transmembrane glycoprotein of the terminal lysosome of African trypanosomes. Its biosynthesis involves transport of an initial gp100 ER precursor to the lysosome, followed by cleavage to N-terminal (gp32) and C-terminal (gp42) subunits that remain non-covalently associated. p67 knockdown is lethal, but the only overt phenotype is an enlarged lysosome (~250 nm to >1000 nm). Orthologues have been characterized in Dictyostelium and mammals. These have processing pathways similar to p67, and are thought to have phospholipase B-like (PLBL) activity. The mouse PLBD2 crystal structure revealed that the PLBLs represent a subgroup of the larger N-terminal Nucleophile (NTN) superfamily, all of which are hydrolases. NTNs activate by internal autocleavage mediated by a nucleophilic residue, i.e., Cys, Ser, or
Thr, on the upstream peptide bond to form N-terminal α (gp32) and C-terminal  β (gp42) subunits that remain non-covalently associated. The N-terminal residue of the β subunit is then catalytic in subsequent hydrolysis reactions. All PLBLs have a conserved Cys/Ser dipeptide at the α/β junction (Cys241/Ser242 in p67), mutation of which renders p67 non-functional in RNAi rescue assays. p67 orthologues are found in many clades of parasitic protozoa, thus p67 is the
founding member of a group of hydrolases that likely play a role broadly in the pathogenesis of parasitic infections.
Original languageEnglish
Number of pages22
VolumeAccepted manuscipt
Early online date19 Oct 2020
Publication statusE-pub ahead of print - 19 Oct 2020


  • Trypanosome
  • Lysosome
  • p67
  • N-terminal nucleophile
  • Phospholipase B-like


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