Zinc coordination by the DHHC cysteine-rich domain of the palmitoyltransferase Swf1

AYELEN GONZALEZ MONTORO; RODRIGO QUIROGA; JAVIER VALDEZ TAUBAS

PORTLAND PRESS LTD

Lugar: Londres; Año: 2013 p. 427 - 427

-acylation, commonly known as palmitoylation, is a widespread post-translational modification of proteins that consists in the tioestherification of one or more cysteine residues with fatty acids. This modification is catalyzed by a family of palmitoyltransferases (PATs), characterized by the presence of a 50-residue long Cysteine-Rich Domain (DHHC-CRD). To gain knowledge on the structure-function relationships of these proteins, we carried out a random-mutagenesis assay designed to uncover essential amino acids in Swf1, the yeast PAT responsible for the palmitoylation of SNARE proteins. We identified 21 novel loss-of-function mutations, which are mostly localized within the DHHC-CRD. Modeling of the tertiary structure of the Swf1 DHHC domain suggests that it could fold as a zinc-finger domain, coordinating two zinc atoms in a CCHC arrangement. All residues predicted to be involved in the coordination of zinc were found to be essential for Swf1 function in the screen. Moreover, the