10779/crick.12708773.v1
Malgorzata Broncel
Malgorzata
Broncel
Caia Dominicus
Caia
Dominicus
Luis Vigetti
Luis
Vigetti
Stephanie D Nofal
Stephanie D
Nofal
Edward J Bartlett
Edward J
Bartlett
Bastien Touquet
Bastien
Touquet
Alex Hunt
Alex
Hunt
Bethan A Wallbank
Bethan A
Wallbank
Stefania Federico
Stefania
Federico
Stephen Matthews
Stephen
Matthews
Joanna C Young
Joanna C
Young
Edward W Tate
Edward W
Tate
Isabelle Tardieux
Isabelle
Tardieux
Moritz Treeck
Moritz
Treeck
Profiling of myristoylation in Toxoplasma gondii reveals an N-myristoylated protein important for host cell penetration.
The Francis Crick Institute
2020
infectious disease
microbiology
Treeck FC001189
Tate - sat
PC
PRT-ack
0601 Biochemistry and Cell Biology
2020-07-24 14:02:08
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Profiling_of_myristoylation_in_Toxoplasma_gondii_reveals_an_N-myristoylated_protein_important_for_host_cell_penetration_/12708773
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.