DHHC2

TgDHHC2 is an inner membrane complex (IMC)-resident palmitoyl S-acyltransferase essential for Toxoplasma gondii tachyzoite survival (PMID:32329212). Conditional disruption causes rapid collapse of the IMC in developing daughter cells and severe morphological defects, while other organelles are mislocalized but still form (PMID:32329212). TgDHHC2 acts sequentially with TgDHHC14 in the construction of distinct IMC sub-compartments, functioning at an earlier step (PMID:32329212). Its catalytic activity maintains the membrane association of the palmitoylated IMC proteins TgISP1, TgISP3, TgIAP1, and TgIAP2, identifying these as its likely palmitoylation substrates (PMID:32329212). Direct acylation of these candidate substrates has not been demonstrated in the available corpus.

1. 2020 High

   Defining where TgDHHC2 acts and what fails without it established that it is an IMC-resident acyltransferase whose loss collapses the IMC during daughter cell formation, distinguishing a biogenesis role from mere protein mislocalization.

   Evidence Fluorescence localization and conditional depletion of TgDHHC2 with imaging of IMC and organelle phenotypes

   PMID:32329212

   Open questions at the time

   • Direct enzymatic acyltransferase activity not biochemically assayed
   • How IMC collapse causes death not mechanistically dissected
2. 2020 High

   Placing TgDHHC2 relative to TgDHHC14 answered whether IMC sub-compartments are built by a single enzyme or a pathway; the two enzymes act sequentially with TgDHHC2 at an earlier step.

   Evidence Conditional depletion with sequential functional analysis of IMC sub-compartment formation

   PMID:32329212

   Open questions at the time

   • Molecular basis of the ordering between DHHC2 and DHHC14 unknown
   • Whether the two enzymes act on overlapping or distinct substrate sets not resolved
3. 2020 Medium

   Identifying which proteins depend on TgDHHC2 addressed its substrate range; loss of membrane association of TgISP1, TgISP3, TgIAP1, and TgIAP2 upon depletion implicated them as its palmitoylation targets.

   Evidence Fractionation/localization of known palmitoylated IMC proteins after conditional depletion of TgDHHC2

   PMID:32329212

   Open questions at the time

   • Substrate inference is indirect — no direct acylation assay performed on the candidate substrates
   • Loss of membrane association could be an indirect consequence of IMC collapse
   • Single lab, not independently confirmed