2LU2

MIC5 regulates the activity of Toxoplasma subtilisin 1 by mimicking a subtilisin prodomain

Summary for 2LU2

• Entry DOI: 10.2210/pdb2lu2/pdb
• NMR Information: BMRB: 18506
• Descriptor: Microneme TgMIC5 protein (1 entity in total)
• Functional Keywords: micronemal protein 5, invasion, pathogenesis, cell adhesion
• Biological source: Toxoplasma gondii
• Total number of polymer chains: 1
• Total formula weight: 15272.90

Authors

Saouros, S.,Dou, Z.,Henry, M.,Marchant, J.,Carruthers, V.B.,Matthews, S. (deposition date: 2012-06-07, release date: 2012-08-22, Last modification date: 2024-05-15)

Primary citation

Saouros, S.,Dou, Z.,Henry, M.,Marchant, J.,Carruthers, V.B.,Matthews, S.
Microneme protein 5 regulates the activity of toxoplasma subtilisin 1 by mimicking a subtilisin prodomain.
J.Biol.Chem., 287:36029-36040, 2012

PubMed Abstract: Toxoplasma 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.

PubMed: 22896704
DOI: 10.1074/jbc.M112.389825

Experimental method

SOLUTION NMR