Dataset Information

Global profiling of myristoylation in Toxoplasma gondii

ABSTRACT: N-myristoylation is a ubiquitous class of protein lipidation across eukaryotes and N-myristoyl transferase (NMT) has been proposed as an attractive drug target in several pathogens. Here we describe the first global chemoproteomic analysis of protein myristoylation in Toxoplasma gondii. Through quantitative mass spectrometry coupled with validated chemoproteomic tools (cleavable capture reagents (Broncel et al., 2015, Speers and Cravatt, 2005) and NMT inhibitor (Schlott et al., 2019)) that allow for experimental validation, we confidently identified 65 myristoylated proteins. This dataset represents a large fraction of the parasite’s myristoylated proteome and a prerequisite to investigate this modification in Toxoplasma.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Toxoplasma Gondii Rh

TISSUE(S): Foreskin Fibroblast, Epithelial Cell Line

DISEASE(S): Toxoplasmosis

SUBMITTER: Malgorzata Broncel

LAB HEAD: Moritz Treeck

PROVIDER: PXD019677 | Pride | 2020-07-06

REPOSITORIES: Pride

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Profiling of myristoylation in Toxoplasma gondii reveals an N-myristoylated protein important for host cell penetration.

Broncel Malgorzata M Dominicus Caia C Vigetti Luis L Nofal Stephanie D SD Bartlett Edward J EJ Touquet Bastien B Hunt Alex A Wallbank Bethan A BA Federico Stefania S Matthews Stephen S Young Joanna C JC Tate Edward W EW Tardieux Isabelle I Treeck Moritz M

eLife 20200703

N-myristoylation is a ubiquitous class of protein lipidation across eukaryotes and N-myristoyl transferase (NMT) has been proposed as an attractive drug target in several pathogens. Myristoylation often primes for subsequent palmitoylation and stable membrane attachment, however, growing evidence suggests additional regulatory roles for myristoylation on proteins. Here we describe the myristoylated proteome of Toxoplasma gondii using chemoproteomic methods and show that a sm ...[more]

PMID: 32618271

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Project description:Rhinovirus causes the common cold and drives exacerbation in asthma and COPD, leading to substantial morbidity and healthcare cost. The single positive strand RNA genome of this non-enveloped virus is translated into a single polyprotein that is processed by virus 3C protease to form three structural capsid proteins VP0, VP1 and VP3, and other proteins required for viral life cycle completion. Capsid proteins assemble into the 5S capsid protomer, five of which form a 14S pentamer, and 12 pentamers then assemble to form the 150S icosahedral provirion into which the viral genome is incorporated. During the final step of viral maturation, VP0 is cleaved into VP2 and VP4. VP4 is encoded at the N-terminus of the viral polyprotein, and in many Picornaviruses is N-myristoylated by host cell N-myristoyltransferase (NMT). We have explored the impact of IMP-1088 (the first sub-nanomolar IC50 dual inhibitor of human N-myristoyl transferases HsNMT1 and HsNMT2) on HRV capsid myristoylation in cells. Global identification of proteins for which myristoylation is selectively inhibited by IMP-1088 was performed by quantitative chemical proteomic analysis of YnMyr-tagged proteins in HeLa cells infected with RV16 treated with 50 nM IMP-1088 or vehicle (DMSO). Proteins were subjected to ligation to AzRB, an azide capture reagent bearing a trypsin-cleavable linker and biotin dual label followed by affinity enrichment on Neutravidin beads, on-bead digestion with trypsin, nanoLC-MS/MS analysis of tryptic peptides, and data processing by label-free protein quantification (LFQ) in MaxQuant. 60 N-myristoylated proteins were identified, including the RV16 polyprotein which responded to IMP-1088 inhibition, with no significant change in protein abundances across the whole proteome in the presence of inhibitor. The majority of viral capsid peptides identified in the pull-down mapped to the VP0 domain of the polyprotein, and the N-terminal YnMyr-tagged peptide was readily identified by MS/MS. These data provide the first direct evidence for HRV capsid myristoylation in human cells, and demonstrate that this lipid modification is highly susceptible to inhibition by a selective NMT inhibitor.

			Action	DRS
	GB_Myr_no_base.raw	Raw
	GB_Myr_no_base_proteome.raw	Raw
	GB_Myr_w_base.raw	Raw
	GB_Myr_w_base_proteome.raw	Raw
	GB_YnMyr_no_base.raw	Raw

Dataset Information

Global profiling of myristoylation in Toxoplasma gondii

Dataset's files

Publications

Profiling of myristoylation in <i>Toxoplasma gondii</i> reveals an <i>N</i>-myristoylated protein important for host cell penetration.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Global profiling of myristoylation in Toxoplasma gondii

Dataset's files

Publications

Profiling of myristoylation in &lt;i&gt;Toxoplasma gondii&lt;/i&gt; reveals an &lt;i&gt;N&lt;/i&gt;-myristoylated protein important for host cell penetration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Profiling of myristoylation in <i>Toxoplasma gondii</i> reveals an <i>N</i>-myristoylated protein important for host cell penetration.