The Canonical DHHC Motif Is Not Absolutely Required For The Activity Of The Yeast S-Acyltransferases Swf1 And Pfa4

AYELEN GONZALEZ MONTORO; SABRNA CHUMPEN RAMIREZ; JAVIER VALDEZ TAUBAS

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 2015 vol. 290 p. 22448 - 22448

rotein S-acyltransferases, also known as palmitoyltransferases (PATs), are characterized by the presence of a 50-amino acid domain called the DHHC domain. Within this domain, these four amino acids constitute a highly conserved motif. It has been proposed that the palmitoylation reaction occurs through a palmitoyl-PAT covalent intermediate that involves the conserved cysteine in the DHHC motif. Mutation of this cysteine results in lack of function for several PATs, and DHHA or DHHS mutants are used regularly as catalytically inactive controls. In a genetic screen to isolate loss-of-function mutations in the yeast PAT Swf1, we isolated an allele encoding a Swf1 DHHR mutant. Overexpression of this mutant is able to partially complement a swf1Δ strain and to acylate the Swf1 substrates Tlg1, Syn8, and Snc1. Overexpression of the palmitoyltransferase Pfa4 DHHA or DHHR mutants also results in palmitoylation of its substrate Chs3. We also investigated the role of the first histidine of