Hemozoin formation in malaria: a two-step process involving histidine-rich proteins and lipids

Pandey, Amit V.; Babbarwal, Vinod K.; Okoyeh, Jude N.; Joshi, Ratan M.; Puri, Sunil K.; Singh, Ram L.; Chauhan, Virander S. (2003). Hemozoin formation in malaria: a two-step process involving histidine-rich proteins and lipids. Biochemical and biophysical research communications, 308(4), pp. 736-743. Academic Press 10.1016/S0006-291X(03)01465-7

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Major blood stage antimalarial drugs like chloroquine and artemisinin target the heme detoxification process of the malaria parasite. Hemozoin formation reactions in vitro using the Plasmodium falciparum histidine-rich protein-2 (Pfhrp-2), lipids, and auto-catalysis are slow and could not explain the speed of detoxification needed for parasite survival. Here, we show that malarial hemozoin formation is a coordinated two component process involving both lipids and histidine-rich proteins. Hemozoin formation efficiency in vitro is 1-2% with Pfhrp-2 and 0.25-0.5% with lipids. We added lipids after 9h in a 12h Pfhrp-2 mediated reaction that resulted in sixfold increase in hemozoin formation. However, a lipid mediated reaction in which Pfhrp-2 was added after 9h produced only twofold increase in hemozoin production compared to the reaction with Pfhrp-2 alone. Synthetic peptides corresponding to the Pfhrp-2 heme binding sequences, based on repeats of AHHAAD, neither alone nor in combination with lipids were able to generate hemozoin in vitro. These results indicate that hemozoin formation in malaria parasite involves both the lipids and the scaffolding proteins. Histidine-rich proteins might facilitate hemozoin formation by binding with a large number of heme molecules, and facilitating the dimer formation involving iron-carboxylate bond between two heme molecules, and lipids may then subsequently assist the mechanism of long chain formation, held together by hydrogen bonds or through extensive networking of hydrogen bonds.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital (discontinued) > Forschungsgruppe Endokrinologie/Diabetologie/Metabolik (Pädiatrie) (discontinued)

UniBE Contributor:

Pandey, Amit Vikram

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0006-291X

Publisher:

Academic Press

Language:

English

Submitter:

Amit Vikram Pandey

Date Deposited:

01 Sep 2014 11:38

Last Modified:

25 Dec 2014 13:31

Publisher DOI:

10.1016/S0006-291X(03)01465-7

PubMed ID:

12927780

BORIS DOI:

10.7892/boris.41748

URI:

https://boris.unibe.ch/id/eprint/41748

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