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How deadly parasites “glide” in human cells

How deadly parasites

Molecular structure of a basic light chain protein in the plasmodium glideosome. Blue “clouds” represent the electron density of a protein, with bonds between the atoms indicated in yellow and the molecular water indicated in red. The crystal structure at 1.5 Å phased by Sulfur-SAD was obtained using the Petra III beam at EMBL Hamburg. Credit: Samuel Paziki / EMBL

Biologically, sliding refers to the type of movement during which the cell moves on the surface without changing its shape. This form of movement is unique to Apicomplexa parasites such as Plasmodium and Toxoplasma. Both parasites, which are transmitted by mosquitoes and cats, have a huge impact on the health of the world. Plasmodium causes 228 million malaria infections and about 400,000 deaths a year. Toxoplasma, which infects as much as a third of the human population, can cause severe symptoms in some people and is especially dangerous during pregnancy.

Sliding allows Apicomplexa parasites to enter and move between host cells. For example, when it enters the human body through a mosquito bite, Plasmodium slides through human skin before passing into human blood vessels. This type of movement relies on actin and myosin, which are the same proteins that allow muscle to move in humans and other vertebrates. Myosin takes the form of molecular “legs” that “march” through the actin filaments and thus create movement.

In Apicomplexa, myosin interacts with several other proteins that together form a complex called the glideosome. The exact mechanism by which glideosomes work is not well understood, among other reasons, as the molecular structure of most glideosomal proteins is unknown. However, understanding this mechanism may help to develop drugs that prevent the assembly of the glideosome and thus stop the progression of diseases such as malaria and toxoplasmosis.

Molecular molds facilitate sliding

Researchers at EMBL Hamburg analyzed the molecular structure of basic light chains (ELCs), which are glideosomal proteins that bind directly to myosin. They are known to be necessary for gliding, but their exact structure and role have been unknown until now. Researchers have now obtained myosin A-linked ELC molecular structures in Toxoplasma gondii and Plasmodium falciparum using X-ray crystallography and magnetic resonance imaging (NMR).

Their study, published in Communication biology, shows that ELCs act as “molecular molds” – after binding myosin A, ELCs become solid and begin to act as its lever arm. This hardening allows the myosin to take longer steps, which probably accelerates the sliding movements of the parasite.

The researchers also investigated the role of calcium, a putative slip regulator, in the interaction between ELC and myosin A. Surprisingly, they found that calcium did not affect the structure of ELC. However, this increases the stability of the ELC-myosin A complex. This unexpected result shows that the architecture of glideosomes still hides many unknowns.

“This work gave a first idea of ​​how these organisms move,” said Matthew Bowler, an EMBL researcher in Grenoble who is not involved in the study, which examines Toxoplasma’s strategies for controlling the immune system after cell invasion. “It’s fascinating to see new molecular details emerge about how these parasites work outside the host cell. The beautiful structures show how the engine that drives this movement is composed and can provide a basis for developing new drugs to treat these diseases. “

Maria Bernabeu, who led a study of vascular dysfunction in cerebral malaria at the EMBL website in Barcelona, ​​added: “Plasmodium transmission through the skin is the first stage of human infection. The advantage of targeting Plasmodium at this stage is that only about a hundred parasites The parasite’s motility can help develop drugs or vaccines that target Plasmodia before it multiplies. “

Interdisciplinary cooperation

The work is the result of interdisciplinary collaboration between structural biologists (Löw group) and parasitologists (Gilberger group) from the European Laboratory of Molecular Biology in Hamburg and the Center for Structural Systems Biology (CSSB), as well as scientists from the Bernhard Nocht Institute for Tropical Plants, University of Hamburg and Martin-Luther-University of Halle-Wittenberg. It demonstrates the potential of interdisciplinary cooperation by contributing to our understanding of biological processes and possible future strategies to combat parasitic diseases.

“Entering malaria research was an exciting endeavor – regular exchanges with experts and an interdisciplinary environment helped us explore the field of parasitology,” says Christian Lev.

Different roles of myosins in “tuning” the cell form for division

More information:
Samuel Paziki et al. Structural role of basic light chains in the apicomplex glideosome, Communication biology (2020). DOI: 10.1038 / s42003-020-01283-8

Provided by the European Molecular Biology Laboratory

Quote: How deadly parasites “slip” into human cells (2020, October 13) extracted on October 14, 2020 from https://phys.org/news/2020-10-deadly-parasites-glide-human-cells .html

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