6RZQ

Plasmodium falciparum Hsp70-x chaperone nucleotide binding domain - ANP-PnP bound state

6RZQ の概要

• エントリーDOI: 10.2210/pdb6rzq/pdb
• 分子名称: Heat shock protein 70, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: malaria exported chaperone intra-erythrocytic amp-pnp, chaperone
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87454.64

構造登録者

Vakonakis, I.,Day, J. (登録日: 2019-06-13, 公開日: 2019-10-02, 最終更新日: 2024-01-24)

主引用文献

Day, J.,Passecker, A.,Beck, H.P.,Vakonakis, I.
ThePlasmodium falciparumHsp70-x chaperone assists the heat stress response of the malaria parasite.
Faseb J., 33:14611-14624, 2019

PubMed Abstract: is the most lethal of human-infective malaria parasites. A hallmark of malaria is extensive remodeling of host erythrocytes by the parasite, which facilitates the development of virulence properties such as host cell adhesion to the endothelial lining of the microvasculature. Host remodeling is mediated by a large complement of parasite proteins exported to the erythrocyte; among them is a single heat shock protein (Hsp)70-class protein chaperone, Hsp70-x (PfHsp70-x). PfHsp70-x was previously shown to assist the development of virulent cytoadherence characteristics. Here, we show that PfHsp70-x also supports parasite growth under elevated temperature conditions that simulate febrile episodes, especially at the beginning of the parasite life cycle when most of host cell remodeling takes place. Biochemical and biophysical analyses of PfHsp70-x, including crystallographic structures of its catalytic domain and the J-domain of its stimulatory Hsp40 cochaperone, suggest that PfHsp70-x is highly similar to human Hsp70 chaperones endogenous to the erythrocyte. Nevertheless, our results indicate that selective inhibition of PfHsp70-x function using small molecules may be possible and highlight specific sites of its catalytic domain as potentially of high interest. We discuss the likely roles of PfHsp70-x and human chaperones in biology and how specific inhibitors may assist us in disentangling their relative contributions.-Day, J., Passecker, A., Beck, H.-P., Vakonakis, I. The Hsp70-x chaperone assists the heat stress response of the malaria parasite.

PubMed: 31690116
DOI: 10.1096/fj.201901741R

実験手法

X-RAY DIFFRACTION (1.81 Å)