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Structure paper

TitleCryo-EM structure of endogenous Pfs230 and Pfs48/45 fertilization complex.
Journal, issue, pagesScience, Vol. 389, Issue 6765, Page eady0241, Year 2025
Publish dateSep 11, 2025
AuthorsMelanie H Dietrich / Jill Chmielewski / Li-Jin Chan / Li Lynn Tan / Amy Adair / Frankie M T Lyons / Mikha Gabriela / Sash Lopaticki / Toby A Dite / Laura F Dagley / Lucia Pazzagli / Priya Gupta / Mohd Kamil / Ashley M Vaughan / Rattanaporn Rojrung / Anju Abraham / Ramin Mazhari / Rhea J Longley / Kathleen Zeglinski / Quentin Gouil / Ivo Mueller / Stewart A Fabb / Rekha Shandre-Mugan / Colin W Pouton / Alisa Glukhova / Shabih Shakeel / Wai-Hong Tham /
PubMed AbstractMalaria parasite fertilization occurs in the midgut of a female mosquito. Blocking fertilization within the mosquito can prevent malaria transmission. Pfs230 and Pfs48/45 proteins are critical for ...Malaria parasite fertilization occurs in the midgut of a female mosquito. Blocking fertilization within the mosquito can prevent malaria transmission. Pfs230 and Pfs48/45 proteins are critical for male fertility and transmission of the malaria parasite. They form a core fertilization complex, but it is unknown how they interact. We determined a cryo-electron microscopy structure of the endogenous Pfs230-Pfs48/45 complex showing that Pfs48/45 interacts with Pfs230 domains 13 and 14. Transgenic parasite lines with these domains removed were defective in Pfs230 gamete localization and showed reduced oocyst formation. Nanobodies against domains 13 and 14 inhibited Pfs230-Pfs48/45 complex formation and reduced transmission, and structural analyses revealed their epitopes. These Pfs230 domains were targets of naturally acquired immunity and immune sera from messenger RNA lipid nanoparticle immunizations blocked parasite transmission.
External linksScience / PubMed:40743371
MethodsEM (single particle) / X-ray diffraction
Resolution1.93 - 4.86 Å
Structure data

48669

9mvt

EMDB-48669: Focused map of Pfs230 domains 1-8 of the endogenous Pfs230-Pfs48/45 complex
PDB-9mvt: Pfs230 domains 1-8 of the endogenous Pfs230-Pfs48/45 complex
Method: EM (single particle) / Resolution: 4.86 Å

EMDB-48670: Focused map of Pfs230 (domains 9-14) and Pfs48/45 of the endogenous Pfs230-Pfs48/45 complex
Method: EM (single particle) / Resolution: 3.34 Å

EMDB-48672: Consensus map of the endogenous Pfs230-Pfs48/45 complex
Method: EM (single particle) / Resolution: 3.36 Å

48673

9mvv

EMDB-48673: Composite map of the endogenous complex of Pfs230-Pfs48/45
PDB-9mvv: Pfs230 (D9-D14) with Pfs48/45 of the endogenous Pfs230-Pfs48/45 complex
Method: EM (single particle) / Resolution: 3.36 Å

PDB-9e7n:
Pfs230 D13D14 in complex with nanobody W2809
Method: X-RAY DIFFRACTION / Resolution: 2.49 Å

PDB-9e7o:
Pfs230 D13D14 in complex with nanobody W2810
Method: X-RAY DIFFRACTION / Resolution: 1.93 Å

PDB-9e7p:
Pfs230 D13D14 in complex with nanobody W2812
Method: X-RAY DIFFRACTION / Resolution: 3.22 Å

Chemicals

ChemComp-GOL:
GLYCEROL

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-PEG:
DI(HYDROXYETHYL)ETHER

ChemComp-HOH:
WATER

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-CIT:
CITRIC ACID

Source
  • plasmodium falciparum (malaria parasite P. falciparum)
  • plasmodium falciparum 3d7 (eukaryote)
  • vicugna pacos (alpaca)
KeywordsPROTEIN BINDING / 6-cysteine protein / Plasmodium falciparum / malaria transmission / nanobody

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