3NEC

Crystal Structure of Toxoplasma gondii Profilin

3NEC の概要

• エントリーDOI: 10.2210/pdb3nec/pdb
• 分子名称: Inflammatory profilin, (2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: actin-binding, profilin, actin-binding protein
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 72798.40

構造登録者

Kucera, K.,Modis, Y. (登録日: 2010-06-08, 公開日: 2010-09-29, 最終更新日: 2024-10-30)

主引用文献

Kucera, K.,Koblansky, A.A.,Saunders, L.P.,Frederick, K.B.,De La Cruz, E.M.,Ghosh, S.,Modis, Y.
Structure-based analysis of Toxoplasma gondii profilin: a parasite-specific motif is required for recognition by Toll-like receptor 11.
J.Mol.Biol., 403:616-629, 2010

PubMed Abstract: Profilins promote actin polymerization by exchanging ADP for ATP on monomeric actin and delivering ATP-actin to growing filament barbed ends. Apicomplexan protozoa such as Toxoplasma gondii invade host cells using an actin-dependent gliding motility. Toll-like receptor (TLR) 11 generates an innate immune response upon sensing T. gondii profilin (TgPRF). The crystal structure of TgPRF reveals a parasite-specific surface motif consisting of an acidic loop, followed by a long β-hairpin. A series of structure-based profilin mutants show that TLR11 recognition of the acidic loop is responsible for most of the interleukin (IL)-12 secretion response to TgPRF in peritoneal macrophages. Deletion of both the acidic loop and the β-hairpin completely abrogates IL-12 secretion. Insertion of the T. gondii acidic loop and β-hairpin into yeast profilin is sufficient to generate TLR11-dependent signaling. Substitution of the acidic loop in TgPRF with the homologous loop from the apicomplexan parasite Cryptosporidium parvum does not affect TLR11-dependent IL-12 secretion, while substitution with the acidic loop from Plasmodium falciparum results in reduced but significant IL-12 secretion. We conclude that the parasite-specific motif in TgPRF is the key molecular pattern recognized by TLR11. Unlike other profilins, TgPRF slows nucleotide exchange on monomeric rabbit actin and binds rabbit actin weakly. The putative TgPRF actin-binding surface includes the β-hairpin and diverges widely from the actin-binding surfaces of vertebrate profilins.

PubMed: 20851125
DOI: 10.1016/j.jmb.2010.09.022

実験手法

X-RAY DIFFRACTION (1.7 Å)