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| Title | Structural elucidation of full-length Pfs48/45 in complex with potent monoclonal antibodies isolated from a naturally exposed individual. |
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| Journal, issue, pages | Nat Struct Mol Biol, Vol. 32, Issue 8, Page 1396-1407, Year 2025 |
| Publish date | May 22, 2025 |
Authors | Iga Kucharska / Danton Ivanochko / Sophia Hailemariam / Maartje R Inklaar / Hee Ryung Kim / Karina Teelen / Rianne Stoter / Marga van de Vegte-Bolmer / Geert-Jan van Gemert / Anthony Semesi / Brandon McLeod / Ahyoung Ki / Won-Kyu Lee / John L Rubinstein / Matthijs M Jore / Jean-Philippe Julien / ![]() |
| PubMed Abstract | Biomedical interventions that block the transmission of Plasmodium falciparum (Pf) from humans to mosquitoes may be critical for malaria elimination. Pfs48/45, a gamete-surface protein essential for ...Biomedical interventions that block the transmission of Plasmodium falciparum (Pf) from humans to mosquitoes may be critical for malaria elimination. Pfs48/45, a gamete-surface protein essential for Pf development in the mosquito midgut, is a target of clinical-stage transmission-blocking vaccines and monoclonal antibodies (mAbs) that disrupt Pf transmission to mosquitoes. Antibodies directed to domain 3 of Pfs48/45 have been structurally and functionally described; however, in-depth information about other inhibitory epitopes on Pfs48/45 is currently limited. Here, we present a cryo-electron microscopy structure of full-length Pfs48/45 in complex with potent human mAbs targeting all three domains. Our data indicate that although Pfs48/45 domains 1 and 2 are rigidly coupled, there is substantial conformational flexibility between domains 2 and 3. Characterization of mAbs against domain 1 revealed the presence of a conformational epitope class that is largely conserved across Pf field isolates and is associated with recognition by potent antibodies. Our study provides insights into epitopes across full-length Pfs48/45 and has implications for the design of next-generation malaria interventions. |
External links | Nat Struct Mol Biol / PubMed:40404982 / PubMed Central |
| Methods | EM (single particle) / X-ray diffraction |
| Resolution | 3.09 - 3.9 Å |
| Structure data | ![]() EMDB-41821: Plasmodium falciparum gametocyte surface protein Pfs48/45 in complex with neutralizing antibodies EMDB-41822, PDB-8u1p: ![]() PDB-8u70: |
| Chemicals | ![]() ChemComp-NAG: |
| Source |
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Keywords | CELL INVASION/Immune System / transmission blocking vaccine / antibody / malaria / CELL INVASION / CELL INVASION-Immune System complex / IMMUNE SYSTEM / Pfs48/45 / human transmission-blocking antibodies |
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homo sapiens (human)
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