Cholesterol bound Plasmodium falciparum co-chaperone 'PFA0660w' complexes with major virulence factor 'PfEMP1' via chaperone 'PfHsp70-x'

Scientific Reports
Ankita BehlPrakash Chandra Mishra

Abstract

Lethality of Plasmodium falciparum caused malaria results from 'cytoadherence', which is mainly effected by exported Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. Several exported P. falciparum proteins (exportome) including chaperones alongside cholesterol rich microdomains are crucial for PfEMP1 translocation to infected erythrocyte surface. An exported Hsp40 (heat shock protein 40) 'PFA0660w' functions as a co-chaperone of 'PfHsp70-x', and these co-localize to specialized intracellular mobile structures termed J-dots. Our studies attempt to understand the function of PFA0660w-PfHsp70-x chaperone pair using recombinant proteins. Biochemical assays reveal that N and C-terminal domains of PFA0660w and PfHsp70-x respectively are critical for their activity. We show the novel direct interaction of PfHsp70-x with the cytoplasmic tail of PfEMP1, and binding of PFA0660w with cholesterol. PFA0660w operates both as a chaperone and lipid binding molecule via its separate substrate and cholesterol binding sites. PfHsp70-x interacts with cholesterol bound PFA0660w and PfEMP1 simultaneously in vitro to form a complex. Collectively, our results and the past literature support the hypothesis that PFA0660w-PfHsp70-x c...Continue Reading

References

Apr 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·K LiberekM Zylicz
Sep 1, 1994·Molecular and Biochemical Parasitology·S BonnefoyO Mercereau-Puijalon
Sep 1, 1993·Protein Science : a Publication of the Protein Society·C Colovos, T O Yeates
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Sep 1, 1997·Molecular and Biochemical Parasitology·A DasN Kumar
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·W C SuhC A Gross
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·T LaufenB Bukau
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Jan 31, 2003·Proteins·Simon C LovellDavid C Richardson
Feb 14, 2003·The Journal of Biological Chemistry·Gowrishankar BanumathyUtpal Tatu
Oct 18, 2003·Molecular and Biochemical Parasitology·Jude M PrzyborskiMichael Lanzer
Apr 7, 2004·European Journal of Biochemistry·Eman BashaElizabeth Vierling
Jun 11, 2005·Journal of Neuroscience Research·Sheng ChenIan R Brown
Jul 1, 2005·Protein Science : a Publication of the Protein Society·Fritha HennessyGregory L Blatch
Apr 13, 2007·The International Journal of Biochemistry & Cell Biology·M BothaG L Blatch
Jun 23, 2007·Nucleic Acids Research·K G TinaN Srinivasan
Apr 12, 2008·Journal of Lipid Research·Daniel Rodriguez-AgudoWilliam M Pandak
Jan 10, 2009·The Journal of Biological Chemistry·Rachna HoraAmit Sharma
Nov 3, 2009·Trends in Parasitology·Tobias Spielmann, Tim-Wolf Gilberger

❮ Previous
Next ❯

Citations

Nov 30, 2019·International Journal of Molecular Sciences·Tawanda Zininga, Addmore Shonhai
Apr 2, 2021·PLoS Pathogens·Josh R Beck, Chi-Min Ho
May 15, 2021·Trends in Parasitology·Thorey K JonsdottirPaul R Gilson
Aug 31, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Margarida Ressurreição, Christiaan van Ooij

❮ Previous
Next ❯

Methods Mentioned

BETA
gel filtration
dot blot
ELISA
pull down
cross linking assay
MDH
protein folding
co-immunoprecipitation
PCR
biosensors

Software Mentioned

Verify 3D
Image J
ERRAT
GraphPad Prism
ImageJ
SPSS
Blastp
RAMPAGE
Octet Data analysis
Swiss

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.