Plasmodium falciparum histidine-rich protein II binds to actin, phosphatidylinositol 4,5-bisphosphate and erythrocyte ghosts in a pH-dependent manner and undergoes coil-to-helix transitions in anionic micelles

Celso Eduardo Benedetti, Jörg Kobarg, Thelma Aguiar Pertinhez, Reynaldo Mascagni Gatti, Osmar Norberto De Souza, Alberto Spisni, Rogério Meneghini

Research output: Contribution to journalArticlepeer-review

Abstract

The recombinant histidine-rich protein II (HRPII) from Plasmodium falciparum was shown to bind actin and phosphatidylinositol 4,5-bisphosphate (PIP2) in vitro in a pH-dependent manner, very similar to hisactophilin, an actin-binding protein from ameba. Binding of HRPII to actin and PIP2 occurred at pH 6.0 and 6.5, but not above pH 7.0. Circular dichroism (CD) spectroscopy confirmed that HRPII interacts with actin at pH below 7.0, as judged by the changes induced in the secondary structure of the HRPII/actin mixture. Further CD analysis demonstrated that HRPII adopts a predominantly α-helical conformation with anionic micelles of PIP2 and SDS, but not with neutral micelles of phosphatidylcholine (PC), a feature that is common to many actin-binding proteins involved in cytoskeleton remodeling. Similarly to hisactophilin, a GFP-HRPII fusion protein shuttled from the cytoplasm to the nucleus of HeLa cells as the cellular pH was lowered from 8.0 to 6.0. HeLa cells transfected with the HRPII gene showed increased levels of histidine-rich proteins (HRPs) in the soluble cell fraction at pH 8.0. At pH 6.0, however, HRPs were detected mainly in the insoluble cell fraction. Interestingly, we found that HRPII binds to human erythrocyte membranes at pH 6.0 and 6.5 but not at pH above 7.0. Our results point to remarkable similarities between HRPII, hisactophilin, and actin-binding proteins. Possible roles of the HRPII during Plasmodium infection are discussed in the light of these findings.

Original languageEnglish
Pages (from-to)157-166
Number of pages10
JournalMolecular and Biochemical Parasitology
Volume128
Issue number2
DOIs
Publication statusPublished - May 2003

Keywords

  • Histidine-rich protein
  • pH-dependent actin-binding
  • pH-sensor protein
  • Phosphatidylinositol 4,5-bisphosphate-binding

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

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