9YGJ

Plasmodium falciparum moving junction staple - PfAMA1, PfRON2, PfRON4, PfRON5

Summary for 9YGJ

• Entry DOI: 10.2210/pdb9ygj/pdb
• EMDB information: 72927
• Descriptor: Rhoptry neck protein 2, Rhoptry neck protein 4, Rhoptry neck protein 5, ... (4 entities in total)
• Functional Keywords: invasion, plasmodium, apicomplexa, cryoem, endogenous, membrane protein
• Biological source: Plasmodium falciparum NF54; More
• Total number of polymer chains: 4
• Total formula weight: 591584.70

Authors

Haile, M.T.,Zhen, J.,Ho, C. (deposition date: 2025-09-29, release date: 2026-07-01, Last modification date: 2026-07-15)

Primary citation

Haile, M.T.,Kaxiras, D.A.,Zhen, J.,Lee, C.L.,Jiang, B.,Small-Saunders, J.L.,Ho, C.M.
Structural basis for host membrane binding and remodeling by invading malaria parasites.
Cell, 2026

PubMed Abstract: 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.

PubMed: 42379167
DOI: 10.1016/j.cell.2026.06.012

Experimental method

ELECTRON MICROSCOPY (3.7 Å)