2WKF

Crystal Structure of Macrophage Migration Inhibitory Factor from Plasmodium falciparum

2WKF の概要

• エントリーDOI: 10.2210/pdb2wkf/pdb
• 関連するPDBエントリー: 2WKB
• 分子名称: MACROPHAGE MIGRATION INHIBITORY FACTOR, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: cytokine
• 由来する生物種: PLASMODIUM FALCIPARUM; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28141.42

構造登録者

Dobson, S.E.,Augustijn, K.D.,Brannigan, J.A.,Dodson, E.J.,Waters, A.P.,Wilkinson, A.J. (登録日: 2009-06-11, 公開日: 2009-10-27, 最終更新日: 2024-11-20)

主引用文献

Dobson, S.E.,Augustijn, K.D.,Brannigan, J.A.,Schnick, C.,Janse, C.J.,Dodson, E.J.,Waters, A.P.,Wilkinson, A.J.
The crystal structures of macrophage migration inhibitory factor from Plasmodium falciparum and Plasmodium berghei.
Protein Sci., 18:2578-2591, 2009

PubMed Abstract: Malaria, caused by Plasmodium falciparum and related parasites, is responsible for millions of deaths each year, mainly from complications arising from the blood stages of its life cycle. Macrophage migration inhibitory factor (MIF), a protein expressed by the parasite during these stages, has been characterized in mammals as a cytokine involved in a broad spectrum of immune responses. It also possesses two catalytic activities, a tautomerase and an oxidoreductase, though the physiological significance of neither reaction is known. Here, we have determined the crystal structure of MIF from two malaria parasites, Plasmodium falciparum and Plasmodium berghei at 2.2 A and 1.8 A, respectively. The structures have an alpha/beta fold and each reveals a trimer, in agreement with the results of analytical ultracentrifugation. We observed open and closed active sites, these being distinguished by movements of proline-1, the catalytic base in the tautomerase reaction. These states correlate with the covalent modification of cysteine 2 to form a mercaptoethanol adduct, an observation confirmed by mass spectrometry. The Plasmodium MIFs have a different pattern of conserved cysteine residues to the mammalian MIFs and the side chain of Cys58, which is implicated in the oxidoreductase activity, is buried. This observation and the evident redox reactivity of Cys2 suggest quite different oxidoreductase characteristics. Finally, we show in pull-down assays that Plasmodium MIF binds to the cell surface receptor CD74, a known mammalian MIF receptor implying that parasite MIF has the ability to interfere with, or modulate, host MIF activity through a competitive binding mechanism.

PubMed: 19827093
DOI: 10.1002/pro.263

実験手法

X-RAY DIFFRACTION (2.05 Å)