Malaria Parasite Caught in the Act of invading into a red blood cell

Good news! Amazing stuff!

Note: Although all authors of this study are affiliated with Columbia University it appears that Columbia University has not published anything about this research. Strange!

"... Now, ... has imaged the moving junction right at the moment of invasion, in unprecedented detail. Her team found that when the Plasmodium parasite installs molecular gaskets in the host cell, it radically remodels the cell membrane to slip through without a trace. This knowledge could help inform the next generation of malaria treatments and influence the drug-discovery process for other parasitic diseases, such as cyclosporiasis and toxoplasmosis. ..."

From the highlights and the abstract:

"Highlights

• Natively assembled AMA1-RON2/4/5 complex isolated from invading Plasmodium merozoites

• Cryo-EM reveals the structure of the basic functional unit of the malarial moving junction

• The malarial moving junction exhibits hallmarks of a membrane-remodeling machine

• Structure-guided design of an invasion-inhibitory protein that blocks AMA1-RON2 binding

Summary

The Plasmodium moving junction is central to malarial host-cell invasion, and yet its function remains unclear.

Here, we determine the endogenous structure of the basic repeating unit of the moving junction, purified directly from invasion-stalled Plasmodium falciparum parasites, revealing a sailboat-shaped 1:1:1:1 assembly of apical membrane antigen 1 (PfAMA1) and rhoptry neck proteins 2, 4, and 5 (PfRON2, PfRON4, and PfRON5).

We observe two PfRON2 transmembrane helices that anchor the complex in the red blood cell (RBC) membrane and display an extracellular handle for PfAMA1 binding.

PfAMA1 directly contacts the RBC membrane, strengthening the connection. PfRON2/4/5 form a large, basic platform inside the RBC that electrostatically engages the RBC membrane and wedges seven amphipathic helices deep into the bilayer, suggesting an active role in host-membrane remodeling.

We then leverage the native membrane context revealed by our structure, along with recent advances in computational protein design, to enable the rational design of a small protein binder that inhibits invasion."

Malaria Parasite Caught in the Act of Breaking and Entering | Quanta Magazine "To invade red blood cells, the deadly protists create temporary molecular portals that disappear behind them — doors we can now see in fine detail."

Structural basis for host membrane binding and remodeling by invading malaria parasites (open access)

Graphical abstract

Figure 1 Global architecture of the P. falciparum moving junction staple