Characterization of plasmodium SEY1, an essential dynamin-like GTPase and potential anti-malarial druggable target
Abstract In some species, SEY1 is a predicted essential dynamin-like GTPase that is implicated in homotypic fusion of endoplasmic reticulum membranes. SEY1 family members are conserved among eukaryotic pathogens, but they show minimal similarity to human atlastins. Here, we characterize Plasmodium SEY1 proteins. Through conditional knockdown and epitope tagging studies in P. falciparum, we demonstrate that SEY1 is essential, localizes within the endoplasmic reticulum, and its disruption leads to defects in endoplasmic reticulum morphology. We show that P. vivax SEY1 can be recombinantly expressed as a soluble truncated isoform. This protein maintains its catalytic activity and ability to dimerize. It also possesses a moderate K d for GTP and is amenable to high throughput inhibition studies. Our data show that SEY1 is a new and attractive druggable and assayable target that is conserved across Plasmodium species.
Authors
- María José Lafuente-Monasterio (ORCID: https://orcid.org/0000-0002-4583-9649)
- Francisco‐Javier Gamo (ORCID: https://orcid.org/0000-0002-1854-2882)
- Wesley C. Van Voorhis A (ORCID: https://orcid.org/0000-0001-6141-2015)
- Dyann F. Wirth (ORCID: https://orcid.org/0000-0002-8604-4455)
- Jeffrey D. Dvorin (ORCID: https://orcid.org/0000-0002-5883-7271)
- Amy E. DeRocher (ORCID: https://orcid.org/0000-0003-1205-7920)
- Sabrina Absalon (ORCID: https://orcid.org/0000-0003-2468-8156)
- Alexander A. Morano
- James Blauwkamp (ORCID: https://orcid.org/0000-0002-7639-2800)
- Krypton Carolino (ORCID: https://orcid.org/0000-0001-6657-0928)
- Madeline A. Farringer (ORCID: https://orcid.org/0000-0002-4821-8397)
- Jean‐Claude Farré (ORCID: https://orcid.org/0000-0001-8785-6474)
- Mariana Laureano de Souza (ORCID: https://orcid.org/0000-0003-1886-3878)
- Elizabeth Harmon (ORCID: https://orcid.org/0000-0002-0017-2705)
- Elizabeth A. Winzeler (ORCID: https://orcid.org/0000-0002-4049-2113)
- Daisy Chen (ORCID: https://orcid.org/0000-0001-6516-7029)
- Sonja Ghidelli‐Disse (ORCID: https://orcid.org/0000-0002-7735-9746)
- Alex Bottome (ORCID: https://orcid.org/0009-0009-3423-946X)
Institutions
- Boston Children's Hospital (US)
- Harvard University (US)
- University of Washington (US)
- University of California San Diego (US)
- GlaxoSmithKline (Germany) (DE)
- GlaxoSmithKline (Spain) (ES)
- Indiana University Indianapolis (US)
- Indiana University School of Medicine (US)
- Seattle Children's Research Institute (US)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-11-02
- DOI
- https://doi.org/10.1038/s41598-026-76796-z
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases