Featured Research

from universities, journals, and other organizations

A new target to inhibit malaria and toxoplasmosis infection

Date:
July 28, 2011
Source:
CNRS (Délégation Paris Michel-Ange)
Summary:
Scientists have characterized a protein complex that allows the agents that cause malaria and toxoplasmosis to infect host cells. This is a highly original mechanism, since the parasite supplies both the receptor which it inserts into the host cell membrane and the ligand it exposes at its surface. The researchers have now shown the three-dimensional structure of this complex. The new data paves the way for new drugs designed to inhibit the formation of the protein complex in question and block invasion by Plasmodium falciparum in red blood cells.

Three-dimensional reconstruction of the RON complex at the junction between Toxoplasma gondii and its host cell as the parasite invades the host cell. The red-coloured ring is the RON2 protein, at the boundary between the intra- and extra-cellular parts of the parasite.
Credit: © researchers at UMR5235 CNRS Université Montpellier 2

Maryse Lebrun, Research Director at Inserm, and her fellow researchers at the Laboratoire Dynamique des interactions membranaires normales et pathologiques (Laboratory of Dynamics of Membrane Interactions in Normal and Pathological Cells -- CNRS/ Montpellier Universities 1 and 2) in France, have characterised a protein complex that allows the agents that cause malaria and toxoplasmosis to infect host cells. This is a highly original mechanism, since the parasite supplies both the receptor which it inserts into the host cell membrane and the ligand it exposes at its surface. The three-dimensional structure of this complex has been now solved in collaboration with Dr. Martin Boulanger (Department of Biochemistry and Microbiology, University of Victoria, in Victoria, British Columbia, Canada).

Related Articles


The new data is published in Science on 22 July 2011. It paves the way for new drugs designed to inhibit the formation of the protein complex in question and block invasion by Plasmodium falciparum in red blood cells.

Apicomplexa form a huge family of parasites that cause many different illnesses in humans and animals, and which includes Plasmodium, the parasite that causes malaria and Toxoplasma gondii, the agent that causes toxoplasmosis. Over a million people die of malaria every year. Over a third of the world's population is at risk and the parasite has developed resistance to most of the anti-malaria drugs currently available. Toxoplasmosis is one of the most widespread congenital infections.

Intracellular parasites such as these penetrate inside the cells of the infected organism. The research laboratory in Montpellier is investigating the mechanisms related to invasion of the host cell, a crucial step in the development of infection, the specific nature of which they want to identify so that new treatment targets can be designed.

Researchers at Inserm and the CNRS recently deciphered the mechanism used by Apicomplexa to penetrate the cell, at cellular and molecul ar level. This involves a protein complex that assembles at the interface between the host cell membrane and the parasite membrane, forming a structure known as a moving junction (MJ). This is a highly original mechanism, since the parasite supplies both the receptor (RON2) which it inserts into the host cell membrane and the ligand (AMA1) which it exposes at its surface. These proteins are not present in the host, so this mechanism is specific to Apicomplexa parasites. The researchers have identified a short-peptide region in RON2 capable of binding AMA1 which has very strong affinity and inhibits invasion by the parasite.

In collaboration with a Canadian team (University of Victoria, Vancouver), the researchers crystallised the AMA1- RON2 peptide complex in Toxoplasma and mapped out the amino acids necessary for AMA1 and RON2 to interact and form the MJ in vivo. The RON2 peptide is inserted into a hydrophobic groove in AMA1, allowing the parasite to overcome the mechanical constraints it encounters as it invades the host cell. "By analysing the relation between structure and function and modelling the equivalent Plasmodium falciparum complex, we were able to identify an area on RON2 that is strongly implicated in the interaction specific to the various Apicomplexa parasites and thus understand the mechanisms used by antibodies targeting AMA1 to inhibit invasion," explained Maryse Lebrun. Together, all this data can be used as the basis for developing dr ugs able to inhibit assembly of the AMA1-RON2 complex and the invasion of red blood cells by P. falciparum.

Furthermore, since the AMA1-RON2 complex is also found for Apicomplexa that cause extremely costly veterinary infections such as avian coccidiosis, piroplasmosis, neosporosis and ovine toxoplasmosis, this strategy can also be applied in treating other parasitic infections. The results of the project may therefore have direct applications in human and veterinary medicine.


Story Source:

The above story is based on materials provided by CNRS (Délégation Paris Michel-Ange). Note: Materials may be edited for content and length.


Journal Reference:

  1. M. L. Tonkin, M. Roques, M. H. Lamarque, M. Pugniere, D. Douguet, J. Crawford, M. Lebrun, M. J. Boulanger. Host Cell Invasion by Apicomplexan Parasites: Insights from the Co-Structure of AMA1 with a RON2 Peptide. Science, 2011; 333 (6041): 463 DOI: 10.1126/science.1204988

Cite This Page:

CNRS (Délégation Paris Michel-Ange). "A new target to inhibit malaria and toxoplasmosis infection." ScienceDaily. ScienceDaily, 28 July 2011. <www.sciencedaily.com/releases/2011/07/110725091428.htm>.
CNRS (Délégation Paris Michel-Ange). (2011, July 28). A new target to inhibit malaria and toxoplasmosis infection. ScienceDaily. Retrieved November 29, 2014 from www.sciencedaily.com/releases/2011/07/110725091428.htm
CNRS (Délégation Paris Michel-Ange). "A new target to inhibit malaria and toxoplasmosis infection." ScienceDaily. www.sciencedaily.com/releases/2011/07/110725091428.htm (accessed November 29, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Saturday, November 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
New Dinosaur Species Found in Museum Collection

New Dinosaur Species Found in Museum Collection

Reuters - Innovations Video Online (Nov. 27, 2014) — A British palaeontologist has discovered a new species of dinosaur while studying fossils in a Canadian museum. Pentaceratops aquilonius was related to Triceratops and lived at the end of the Cretaceous Period, around 75 million years ago. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Tryptophan Isn't Making You Sleepy On Thanksgiving

Tryptophan Isn't Making You Sleepy On Thanksgiving

Newsy (Nov. 27, 2014) — Tryptophan, a chemical found naturally in turkey meat, gets blamed for sleepiness after Thanksgiving meals. But science points to other culprits. Video provided by Newsy
Powered by NewsLook.com
Classic Hollywood Memorabilia Goes Under the Hammer

Classic Hollywood Memorabilia Goes Under the Hammer

Reuters - Entertainment Video Online (Nov. 26, 2014) — The iconic piano from "Casablanca" and the Cowardly Lion suit from "The Wizard of Oz" fetch millions at auction. Sara Hemrajani reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins