Structural highlights
Publication Abstract from PubMedToxoplasma gondii is the model parasite of the phylum Apicomplexa, which contains obligate intracellular parasites of medical and veterinary importance. Apicomplexans invade host cells by a multistep process involving the secretion of adhesive microneme protein (MIC) complexes. The subtilisin protease TgSUB1 trims several MICs on the parasite surface to activate gliding motility and host invasion. Although a previous study showed that expression of the secretory protein TgMIC5 suppresses TgSUB1 activity, the mechanism was unknown. Here, we solve the three-dimensional structure of TgMIC5 by nuclear magnetic resonance (NMR), revealing that it mimics a subtilisin prodomain including a flexible C-terminal peptide that may insert into the subtilisin active site. We show that TgMIC5 is an almost 50-fold more potent inhibitor of TgSUB1 activity than the small molecule inhibitor N-[N-(N-acetyl-l-leucyl)-l-leucyl]-l-norleucine (ALLN). Moreover, we demonstrate that TgMIC5 is retained on the parasite plasma membrane via its physical interaction with the membrane-anchored TgSUB1. Microneme protein 5 regulates the activity of toxoplasma subtilisin 1 by mimicking a subtilisin prodomain.,Saouros S, Dou Z, Henry M, Marchant J, Carruthers VB, Matthews S J Biol Chem. 2012 Oct 19;287(43):36029-40. doi: 10.1074/jbc.M112.389825. Epub, 2012 Aug 15. PMID:22896704[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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