The Golgi S-acylation machinery comprises zDHHC enzymes with major differences in substrate affinity and S-acylation activity

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Lemonidis, Kimon and Gorleku, Oforiwa A. and Sanchez Perez, Maria C. and Grefen, Christopher and Chamberlain, Luke H. (2014) The Golgi S-acylation machinery comprises zDHHC enzymes with major differences in substrate affinity and S-acylation activity. Molecular Biology of the Cell, 25 (24). pp. 3870-3883. ISSN 1059-1524 (https://doi.org/10.1091/mbc.E14-06-1169)

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Abstract

S-acylation, the attachment of fatty acids onto cysteine residues, regulates protein trafficking and function, and is mediated by a family of “zDHHC” enzymes. The S-acylation of peripheral membrane proteins has been proposed to occur at the Golgi, catalysed by an S-acylation “machinery” that displays little substrate specificity. To advance understanding of how S-acylation of peripheral membrane proteins is handled by Golgi zDHHC enzymes, we have investigated interactions between a subset of four Golgi zDHHC enzymes and two S-acylated proteins, SNAP25 and Cysteine-String Protein (CSP). Our results uncover major differences in substrate recognition and S-acylation by these zDHHC enzymes. The Ankyrin-repeat (ANK) domains of zDHHC17 and zDHHC13 mediated strong and selective interactions with SNAP25/CSP, whereas binding of zDHHC3 and zDHHC7 to these proteins was barely detectable. Despite this, zDHHC3/zDHHC7 could S-acylate SNAP25/CSP more efficiently than zDHHC17, whereas zDHHC13 lacked S-acylation activity toward these proteins. Overall, the results of this study support a model whereby dynamic intracellular localisation of peripheral membrane proteins is achieved by highly selective recruitment by a subset of zDHHC enzymes at the Golgi, combined with highly efficient S-acylation by other Golgi zDHHC-enzymes.

ORCID iDs

Lemonidis, Kimon ORCID logoORCID: https://orcid.org/0000-0003-1332-6002, Gorleku, Oforiwa A., Sanchez Perez, Maria C., Grefen, Christopher and Chamberlain, Luke H. ORCID logoORCID: https://orcid.org/0000-0002-8701-4995;
CORE (COnnecting REpositories)