Brown_2022_Pathogens_11_1245

Reference

Title : Trypanosoma brucei Acyl-Protein Thioesterase-like (TbAPT-L) Is a Lipase with Esterase Activity for Short and Medium-Chain Fatty Acids but Has No Depalmitoylation Activity - Brown_2022_Pathogens_11_1245
Author(s) : Brown RWB , Sharma AI , Villanueva MR , Li X , Onguka O , Zilbermintz L , Nguyen H , Falk BA , Olson CL , Taylor JM , Epting CL , Kathayat RS , Amara N , Dickinson BC , Bogyo M , Engman DM
Ref : Pathogens , 11 : , 2022
Abstract : Dynamic post-translational modifications allow the rapid, specific, and tunable regulation of protein functions in eukaryotic cells. S-acylation is the only reversible lipid modification of proteins, in which a fatty acid, usually palmitate, is covalently attached to a cysteine residue of a protein by a zDHHC palmitoyl acyltransferase enzyme. Depalmitoylation is required for acylation homeostasis and is catalyzed by an enzyme from the alpha/beta hydrolase family of proteins usually acyl-protein thioesterase (APT1). The enzyme responsible for depalmitoylation in Trypanosoma brucei parasites is currently unknown. We demonstrate depalmitoylation activity in live bloodstream and procyclic form trypanosomes sensitive to dose-dependent inhibition with the depalmitoylation inhibitor, palmostatin B. We identified a homologue of human APT1 in Trypanosoma brucei which we named TbAPT-like (TbAPT-L). Epitope-tagging of TbAPT-L at N- and C- termini indicated a cytoplasmic localization. Knockdown or over-expression of TbAPT-L in bloodstream forms led to robust changes in TbAPT-L mRNA and protein expression but had no effect on parasite growth in vitro, or cellular depalmitoylation activity. Esterase activity in cell lysates was also unchanged when TbAPT-L was modulated. Unexpectedly, recombinant TbAPT-L possesses esterase activity with specificity for short- and medium-chain fatty acid substrates, leading to the conclusion, TbAPT-L is a lipase, not a depalmitoylase.
ESTHER : Brown_2022_Pathogens_11_1245
PubMedSearch : Brown_2022_Pathogens_11_1245
PubMedID: 36364996
Gene_locus related to this paper: tryb2-q7yxi0

Related information

Gene_locus related to this paper: tryb2-q7yxi0

Citations formats

Brown RWB, Sharma AI, Villanueva MR, Li X, Onguka O, Zilbermintz L, Nguyen H, Falk BA, Olson CL, Taylor JM, Epting CL, Kathayat RS, Amara N, Dickinson BC, Bogyo M, Engman DM (2022)
Trypanosoma brucei Acyl-Protein Thioesterase-like (TbAPT-L) Is a Lipase with Esterase Activity for Short and Medium-Chain Fatty Acids but Has No Depalmitoylation Activity
Pathogens 11 :

Brown RWB, Sharma AI, Villanueva MR, Li X, Onguka O, Zilbermintz L, Nguyen H, Falk BA, Olson CL, Taylor JM, Epting CL, Kathayat RS, Amara N, Dickinson BC, Bogyo M, Engman DM (2022)
Pathogens 11 :