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.