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TitleStructural basis for host membrane binding and remodeling by invading malaria parasites.
Journal, issue, pagesCell, Year 2026
Publish dateJun 30, 2026
AuthorsMeseret T Haile / Daphne A Kaxiras / James Zhen / Carolyn L Lee / Britney Jiang / Jennifer L Small-Saunders / Chi-Min Ho /
PubMed AbstractThe 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 ...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.
External linksCell / PubMed:42379167 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 4.1 Å
Structure data

72927

9ygj

EMDB-72927, PDB-9ygj:
Plasmodium falciparum moving junction staple - PfAMA1, PfRON2, PfRON4, PfRON5
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-72928: Plasmodium falciparum moving junction staple - Consensus map of PfRON2,PfRON4,PfRON5
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-72929: Plasmodium falciparum moving junction staple - Particle subtracted, local refined PfAMA1
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-72930: Plasmodium falciparum moving junction staple - Particle subtracted, local refined C-terminus of PfRON5
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-72931: Plasmodium falciparum moving junction staple - Particle subtracted, local refined C-terminus of PfRON5 (alternative)
Method: EM (single particle) / Resolution: 3.4 Å

Source
  • plasmodium falciparum nf54 (eukaryote)
KeywordsMEMBRANE PROTEIN / Invasion / Plasmodium / Apicomplexa / CryoEM / Endogenous

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