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

Diamond Keywords: Malaria

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography

Added On: 05/10/2020 09:31

Discipline Tags:

Infectious Diseases Disease in the Developing World Health & Wellbeing Biochemistry Chemistry Structural biology Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)