The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase

doi:10.1083/jcb.200206120

Published online 7 October 2002. doi:10.1083/jcb.200206120

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The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase

Amy F. Roth¹, Ying Feng², Linyi Chen² and Nicholas G. Davis¹^,2

¹ Department of Surgery, Wayne State University School of Medicine, Detroit, MI 48201
² Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201

Address correspondence to Nicholas G. Davis, Departments of Surgery and Pharmacology, Wayne State University School of Medicine, Elliman Building, Room 1205, 421 E. Canfield, Detroit, MI 48201. Tel.: (313) 577-7807. Fax: (313) 577-7642. E-mail: ndavis{at}cmb.biosci.wayne.edu

Protein palmitoylation has been long appreciated for its rolein tethering proteins to membranes, yet the enzymes responsiblefor this modification have eluded identification. Here, experimentsin vivo and in vitro demonstrate that Akr1p, a polytopic membraneprotein containing a DHHC cysteine-rich domain (CRD), is a palmitoyltransferase (PTase). In vivo, we find that the casein kinaseYck2p is palmitoylated and that Akr1p function is required forthis modification. Akr1p, purified to near homogeneity fromyeast membranes, catalyzes Yck2p palmitoylation in vitro, indicatingthat Akr1p is itself a PTase. Palmitoylation is stimulated byadded ATP. Furthermore, during the reaction, Akr1p is itselfpalmitoylated, suggesting a role for a palmitoyl-Akr1p intermediatein the overall reaction mechanism. Mutations introduced intothe Akr1p DHHC-CRD eliminate both the trans- and autopalmitoylationactivities, indicating a central participation of this conservedsequence in the enzymatic reaction. Finally, our results indicatethat palmitoylation within the yeast cell is controlled by multiplePTase specificities. The conserved DHHC-CRD sequence, we propose,is the signature feature of an evolutionarily widespread PTasefamily.

Key Words: acylation; Saccharomyces cerevisiae; palmitoyl coenzyme A; Akr1p protein; acyltransferases

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