Bartlett, Edward J.

Broncel, Malgorzata

Dominicus, Caia

Federico, Stefania

Hunt, Alex

Matthews, Stephen

Nofal, Stephanie D.

Tardieux, Isabelle

Tate, Edward W.

Touquet, Bastien

Treeck, Moritz

Vigetti, Luis

Wallbank, Bethan A.

Young, Joanna C.

English

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 small-molecule NMT inhibitor developed against related Plasmodium spp. is also functional in Toxoplasma. We identify myristoylation on a transmembrane protein, the microneme protein 7 (MIC7), which enters the secretory pathway in an unconventional fashion with the myristoylated N-terminus facing the lumen of the micronemes. MIC7 and its myristoylation play a crucial role in the initial steps of invasion, likely during the interaction with and penetration of the host cell. Myristoylation of secreted eukaryotic proteins represents a substantial expansion of the functional repertoire of this co-translational modification.</p

Edinburgh Research Explorer

Profiling of myristoylation in toxoplasma gondii reveals an n-myristoylated protein important for host cell penetration

Malgorzata Broncel

Caia Dominicus

Luis Vigetti

Stephanie D Nofal

Edward J Bartlett

Bastien Touquet

Alex Hunt

Bethan A Wallbank

Stefania Federico

Stephen Matthews

Joanna C Young

Edward W Tate

Isabelle Tardieux

Moritz Treeck

Crossref

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

https://www.research.ed.ac.uk/files/236797588/elife_57861_v2.pdf

Profiling of myristoylation in toxoplasma gondii reveals an n-myristoylated protein important for host cell penetration

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