2LU2

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

2LU2 の概要

• エントリーDOI: 10.2210/pdb2lu2/pdb
• NMR情報: BMRB: 18506
• 分子名称: Microneme TgMIC5 protein (1 entity in total)
• 機能のキーワード: micronemal protein 5, invasion, pathogenesis, cell adhesion
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15272.90

構造登録者

Saouros, S.,Dou, Z.,Henry, M.,Marchant, J.,Carruthers, V.B.,Matthews, S. (登録日: 2012-06-07, 公開日: 2012-08-22, 最終更新日: 2024-05-15)

主引用文献

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

実験手法

SOLUTION NMR