Anthrax toxin requires ZDHHC5-mediated palmitoylation of its surface-processing host enzymes

Sergeeva, Oksana A.; Goot, F. Gisou van der

doi:10.1073/pnas.1812588116

Cited by 26 publications

(39 citation statements)

References 65 publications

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“…In both HEK293 and A549 cells, it interacts with two Golgi-localized proteins, ZDHHC5 and GOLGA7 (Gordon et al, 2020;Stukalov et al, 2020), which form a complex localized to the plasma membrane (Ko and Dixon, 2018;Ohno et al, 2006). ZDHHC5 is an acyltransferase that can localize to the ER, Golgi apparatus, and plasma membrane and controls Golgi trafficking and palmitoylation of anthrax toxin (Sergeeva and van der Goot, 2019). GOLGA7 is a Golgin subfamily member that assists ZDHHC5 activity on the plasma membrane (Ko et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Role of the early secretory pathway in SARS-CoV-2 infection

Sicari

Chatziioannou

Κουτσανδρέας

et al. 2020

Journal of Cell Biology

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Similar to other RNA viruses, SARS-CoV-2 must (1) enter a target/host cell, (2) reprogram it to ensure its replication, (3) exit the host cell, and (4) repeat this cycle for exponential growth. During the exit step, the virus hijacks the sophisticated machineries that host cells employ to correctly fold, assemble, and transport proteins along the exocytic pathway. Therefore, secretory pathway–mediated assemblage and excretion of infective particles represent appealing targets to reduce the efficacy of virus biogenesis, if not to block it completely. Here, we analyze and discuss the contribution of the molecular machines operating in the early secretory pathway in the biogenesis of SARS-CoV-2 and their relevance for potential antiviral targeting. The fact that these molecular machines are conserved throughout evolution, together with the redundancy and tissue specificity of their components, provides opportunities in the search for unique proteins essential for SARS-CoV-2 biology that could also be targeted with therapeutic objectives. Finally, we provide an overview of recent evidence implicating proteins of the early secretory pathway as potential antiviral targets with effective therapeutic applications.

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Section: Introductionmentioning

confidence: 99%

Role of the early secretory pathway in SARS-CoV-2 infection

Sicari

Chatziioannou

Κουτσανδρέας

et al. 2020

Journal of Cell Biology

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“…Palmitoylation has been reported to facilitate membrane fusion by SARS-CoV Spike and suggests a potential target for therapeutic inhibition 36 . Interestingly, ZDHHC5 also has a published role in allowing anthrax toxin to enter cells, suggesting that inhibition of this enzyme could have broad utility 37 . Host interactions of Nsp8 (signal recognition particle), Orf8 (endoplasmic reticulum quality control), M (ER structural morphology proteins), Nsp13 (golgins) may facilitate the dramatic reconfiguration of ER/Golgi trafficking during coronavirus infection, and interactions in peripheral compartments by Nsp6 and M (vacuolar ATPase), Nsp7 (Rabs), Nsp10 (AP2), E (AP3), and Orf3a (HOPS) may also modify endomembrane compartments to favor coronavirus replication.…”

Section: The Sars-cov-2 Interactome Reveals Novel Aspects Of Sars-covmentioning

confidence: 99%

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

Gordon¹,

Jang²,

Bouhaddou³

et al. 2020

Preprint

425

586

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ABSTRACTAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.

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“…On the other hand, zDHHC5 can also localize intracellularly to sorting and recycling endosomes, possibly overlapping with the distribution of flotillins. Furthermore, zDHHC5 has been shown to affect several aspects of the Golgi-plasma membrane-endosome trafficking of proteins [115,116]. The most comprehensive picture of the zDHHC5 localization, its substrates, and functions concerns neurons.…”

Section: Flotillin-mediated Endocytosis Requires Protein S-palmitoylamentioning

confidence: 99%

Flotillins: At the Intersection of Protein S-Palmitoylation and Lipid-Mediated Signaling

Kwiatkowska

Matveichuk

Fronk

et al. 2020

IJMS

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Flotillin-1 and flotillin-2 are ubiquitously expressed, membrane-associated proteins involved in multifarious cellular events from cell signaling, endocytosis, and protein trafficking to gene expression. They also contribute to oncogenic signaling. Flotillins bind the cytosolic leaflet of the plasma membrane and endomembranes and, upon hetero-oligomerization, serve as scaffolds facilitating the assembly of multiprotein complexes at the membrane–cytosol interface. Additional functions unique to flotillin-1 have been discovered recently. The membrane-binding of flotillins is regulated by S-palmitoylation and N-myristoylation, hydrophobic interactions involving specific regions of the polypeptide chain and, to some extent, also by their oligomerization. All these factors endow flotillins with an ability to associate with the sphingolipid/cholesterol-rich plasma membrane domains called rafts. In this review, we focus on the critical input of lipids to the regulation of the flotillin association with rafts and thereby to their functioning. In particular, we discuss how the recent developments in the field of protein S-palmitoylation have contributed to the understanding of flotillin1/2-mediated processes, including endocytosis, and of those dependent exclusively on flotillin-1. We also emphasize that flotillins affect directly or indirectly the cellular levels of lipids involved in diverse signaling cascades, including sphingosine-1-phosphate and PI(4,5)P2. The mutual relations between flotillins and distinct lipids are key to the regulation of their involvement in numerous cellular processes.

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Anthrax toxin requires ZDHHC5-mediated palmitoylation of its surface-processing host enzymes

Cited by 26 publications

References 65 publications

Role of the early secretory pathway in SARS-CoV-2 infection

Role of the early secretory pathway in SARS-CoV-2 infection

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

Flotillins: At the Intersection of Protein S-Palmitoylation and Lipid-Mediated Signaling

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