gms | German Medical Science

12th Malaria Meeting

Malaria Group / Section Antiparasitic Chemotherapy of the Paul-Ehrlich-Society (PEG e. V.) in cooperation with the German Society for Tropical Medicine and International Health (DTG e. V.) and the German Society for Parasitology (DGP e. V.)

14.11. - 15.11.2014, Bonn

A putative G-protein from P. falciparum chemical properties and characterization of the protein

Meeting Abstract

  • Annette Kaiser - Medical Research Centre, University Duisburg-Essen, Essen, Germany
  • Barbara Langer - Medical Research Centre, University Duisburg-Essen, Essen, Germany
  • David Kersting - Medical Research Centre, University Duisburg-Essen, Essen, Germany
  • Mirko Krüger - Medical Research Centre, University Duisburg-Essen, Essen, Germany

12th Malaria Meeting. Bonn, 14.-15.11.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc14mal05

doi: 10.3205/14mal05, urn:nbn:de:0183-14mal050

Published: December 17, 2014

© 2014 Kaiser et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



During its development the malaria parasite P. falciparum has to adapt to various different environmental contexts like the blood stream, the human liver and the midgut of the mosquito. Key cellular mechanisms involving G-protein coupled signal transduction chains are assumed to act at these interfaces. Previous findings showed that the parasite uses the G-protein from the human host for invasion. We here describe the first cloning and expression of a putative guanine-nucleotide-binding protein (G-protein) from Plasmodium.

The protein reveals an open reading frame of 2733 bp encoding a protein of 911 amino acids and has a theoretical pI of 8.68 and a molecular weight of 108.57 kDa. Transcript formation and expression are significantly increased in the late developmental stages during schizont and gametocyte formation in the erythrocytic phase. Most notably, the G-protein has GTP binding capacity and Gtpase activity due to an EngA domain which is also present in small Ras-like Gtpases in a variety of Bacillus species and Mycobacteria. By contrast, P. falciparum G-protein is divergent from any human alpha-subunit. The G-protein was expressed in E. coli as a histidine-tagged fusion protein with a short half life of 3.5 hours. Purification was only possible under native conditions by Nickel-chelate chromatography and separation by Blue Native page gel electrophoresis. Binding of a fluorescent GTP analogue BODIPY® FL guanosine 5’O-(thiotriphosphate) was determined by fluorescence emission. Mastoparan stimulated GTP binding in the presence of Mg2+. The determined Gtpase activity of the human paralogue was 50% higher than the activity of the parasitic enzyme.

In light of these significant results a non-canonical signaling pathway via a non-heterotrimeric G-protein seems to be present in Plasmodium. A current research for the more prevalent receptor will delineate this pathway with respect to transmission and relevance to antimalarial chemotherapy.