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p67 : a cryptic lysosomal hydrolase in trypanosoma brucei?
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dc.contributor.author | Koeller, Carolina M. | |
dc.contributor.author | Smith, Terry K. | |
dc.contributor.author | Gulick, Andrew M. | |
dc.contributor.author | Bangs, James D. | |
dc.date.accessioned | 2021-04-18T23:47:59Z | |
dc.date.available | 2021-04-18T23:47:59Z | |
dc.date.issued | 2020-10-19 | |
dc.identifier | 271053353 | |
dc.identifier | 362788ec-0497-415c-b4cf-d9fcd1219f53 | |
dc.identifier | 85096068125 | |
dc.identifier | 000674635600016 | |
dc.identifier.citation | Koeller , C M , Smith , T K , Gulick , A M & Bangs , J D 2020 , ' p67 : a cryptic lysosomal hydrolase in trypanosoma brucei ? ' , Parasitology , vol. Accepted manuscipt . https://doi.org/10.1017/S003118202000195X | en |
dc.identifier.issn | 0031-1820 | |
dc.identifier.other | RIS: urn:B104E0782625CDE2DE74F38FDE12EB1E | |
dc.identifier.uri | https://hdl.handle.net/10023/23048 | |
dc.description | Funding: This work was supported by United States Public Health Service Grants R01 AI056866 to JDB, and by support of the Jacobs School of Medicine and Biomedical Sciences. | en |
dc.description.abstract | 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. | |
dc.format.extent | 22 | |
dc.format.extent | 1520697 | |
dc.language.iso | eng | |
dc.relation.ispartof | Parasitology | en |
dc.subject | Trypanosome | en |
dc.subject | Lysosome | en |
dc.subject | p67 | en |
dc.subject | N-terminal nucleophile | en |
dc.subject | Phospholipase B-like | en |
dc.subject | QH301 Biology | en |
dc.subject | QR Microbiology | en |
dc.subject | T-NDAS | en |
dc.subject.lcc | QH301 | en |
dc.subject.lcc | QR | en |
dc.title | p67 : a cryptic lysosomal hydrolase in trypanosoma brucei? | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | https://doi.org/10.1017/S003118202000195X | |
dc.description.status | Peer reviewed | en |
dc.date.embargoedUntil | 2021-04-19 |
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