Structure and Mechanism of DHHC Protein Acyltransferases

Stix, Robyn; Lee, Chul‐Jin; Faraldo‐Gómez, José D.; Banerjee, Anirban

doi:10.1016/j.jmb.2020.05.023

Cited by 50 publications

(38 citation statements)

References 115 publications

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“…This observation suggests that the first histidine may be important for activating the protein substrate rather than the DHHC active-site cysteine. Another possible explanation is a different mechanism driven by the prerequisite of Erf2 for its binding partner Erf4 for enzymatic activity [ 10 , 35 ]. Interestingly, zDHHC13 uniquely possesses a natural DQHC in place of a DHHC motif.…”

Section: The Zdhhc Family Of Protein Acyltransferasesmentioning

confidence: 99%

“…We will first provide an overview of the shared structure and mechanism within this enzyme family, then outline approaches to identify substrates for individual zDHHC proteins and discuss the mechanisms that underlie substrate recruitment. For a detailed look at the structure and mechanism of zDHHC-mediated palmitoylation, the reader is referred to [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

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Substrate recruitment by zDHHC protein acyltransferases

Malgapo

Linder

2021

Open Biol.

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Protein palmitoylation is the post-translational attachment of fatty acids, most commonly palmitate (C16 : 0), onto a cysteine residue of a protein. This reaction is catalysed by a family of integral membrane proteins, the zDHHC protein acyltransferases (PATs), so-called due to the presence of an invariant Asp–His–His–Cys (DHHC) cysteine-rich domain harbouring the catalytic centre of the enzyme. Conserved throughout eukaryotes, the zDHHC PATs are encoded by multigene families and mediate palmitoylation of thousands of protein substrates. In humans, a number of zDHHC proteins are associated with human diseases, including intellectual disability, Huntington's disease, schizophrenia and cancer. Key to understanding the physiological and pathophysiological importance of individual zDHHC proteins is the identification of their protein substrates. Here, we will describe the approaches and challenges in assigning substrates for individual zDHHCs, highlighting key mechanisms that underlie substrate recruitment.

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Section: The Zdhhc Family Of Protein Acyltransferasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Substrate recruitment by zDHHC protein acyltransferases

Malgapo

Linder

2021

Open Biol.

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“…Although S-acyl groups of some proteins do not turn over or they do it at a very low rate, some other proteins, such as the Ras isoforms, show a very rapid cycling. Thus, after palmitoylation at the Golgi by palmitoyl acyl transferases (PATs) ( Stix et al, 2020 ), N/H-Ras are transferred to the plasma membrane (PM) via the secretory pathway. In their way to the PM, fully palmitoylated and active H-/N-Ras can also localize at recycling endosomes ( Misaki et al, 2010 ).…”

Section: Subcellular Localization and Functionmentioning

confidence: 99%

Palmitoylation as a Key Regulator of Ras Localization and Function

Busquets-Hernández

Triola

2021

Front. Mol. Biosci.

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Ras proteins require membrane association for proper function. This process is tightly regulated by reversible palmitoylation that controls not only the distribution over different subcellular compartments but also Ras compartmentalization within membrane subdomains. As a result, there is a growing interest in protein palmitoylation and the enzymes that control this process. In this minireview, we discuss how palmitoylation affects the localization and function of Ras proteins. A better understanding of the regulatory mechanism controlling protein lipidation is expected to provide new insights into the functional role of these modifications and may ultimately lead to the development of novel therapeutic approaches.

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“…Protein palmitoylation is catalyzed by palmitoyl acyltransferases (PATs), also known as DHHC proteins containing a highly conserved zinc finger Asp–His–His–Cys motif as their catalytic center [ 26 , 27 ]. DHHCs catalyze protein palmitoylation through a two-step reaction.…”

Section: Introductionmentioning

confidence: 99%

“…The first step is auto-palmitoylation in which the DHHC protein transfers palmitate from palmitoyl-CoA to itself. Then, the enzyme transfers palmitate from itself onto the substrate protein [ 26 , 28 ]. In mammals, a family of 23 DHHC enzymes family has been identified [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Palmitoylation of the Bovine Foamy Virus Envelope Glycoprotein Is Required for Viral Replication

Chai

Wang

et al. 2020

Viruses

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Membrane proteins of enveloped viruses have been reported to undergo palmitoylation, a post-translational modification often having a critical role in the function of these viral proteins and hence viral replication. In this study, we report that the foamy virus (FV) envelope (Env) glycoprotein is palmitoylated. Specifically, we found that bovine foamy virus (BFV) Env (BEnv) is palmitoylated at amino acid positions C58 and C59 by BDHHC3 and BDHHC20 in a DHHC motif-dependent manner. In addition, mutations C58S and C58/59S significantly decrease cell surface expression of BEnv, subviral particle (SVP) egress, and its membrane fusion activity, thus ultimately inhibiting BFV replication. The C59S mutation exerts a minor effect in this regard. Taken together, these data demonstrate that the function of BEnv in the context of BFV replication is under the regulation of palmitoylation.

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Structure and Mechanism of DHHC Protein Acyltransferases

Cited by 50 publications

References 115 publications

Substrate recruitment by zDHHC protein acyltransferases

Substrate recruitment by zDHHC protein acyltransferases

Palmitoylation as a Key Regulator of Ras Localization and Function

Palmitoylation of the Bovine Foamy Virus Envelope Glycoprotein Is Required for Viral Replication

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