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Structure of the substrate-binding domain of Plasmodium falciparum heat-shock protein 70-x
DOI:
10.1107/S2053230X2001208X
Authors:
Julia
Schmidt
(University of Oxford)
,
Ioannis
Vakonakis
(University of Oxford)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Acta Crystallographica Section F Structural Biology Communications
, VOL 76
, PAGES 495 - 500
State:
Published (Approved)
Published:
October 2020
Diamond Proposal Number(s):
18069

Abstract: The malaria parasite Plasmodium falciparum extensively modifies erythrocytes that it invades by exporting a large complement of proteins to the host cell. Among these exported components is a single heat-shock 70 kDa class protein, PfHsp70-x, that supports the virulence and growth rate of the parasite during febrile episodes. The ATP-binding domain of PfHsp70-x has previously been resolved and showed the presence of potentially druggable epitopes that differ from those on human Hsp70 chaperones. Here, the crystallographic structure of the substrate-binding domain (SBD) of PfHsp70-x is presented in complex with a hydrophobic peptide. The PfHsp70-x SBD is shown to be highly similar to the counterpart from a human erythrocytic Hsp70 chaperone. The binding of substrate at the interface between β-sandwich and α-helical subdomains of this chaperone segment is also conserved between the malaria parasite and humans. It is hypothesized that the parasite may partly exploit human chaperones for intra-erythrocytic trafficking and maintenance of its exported proteome.
Journal Keywords: malaria; chaperones; Plasmodium falciparum; erythrocyte remodelling; PfHsp70-x; PfEMP-1; crystallography; complexes
Subject Areas:
Biology and Bio-materials,
Medicine
Instruments:
I03-Macromolecular Crystallography