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

Kimon Lemonidis, Oforiwa A. Gorleku, Maria C. Sanchez Perez, Christopher Grefen, Luke H. Chamberlain

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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.
Original languageEnglish
Pages (from-to)3870-3883
Number of pages14
JournalMolecular Biology of the Cell
Volume25
Issue number24
Early online date24 Sep 2014
DOIs
Publication statusPublished - 1 Dec 2014

Keywords

  • S-acylation
  • cysteine residues
  • protein trafficking
  • protein function
  • Golgi zDHHC-enzymes

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