PXD060667-1

PXD060667 is an original dataset announced via ProteomeXchange.

Title	Cryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complex
Description	Plasmodium falciparum Pfs230 and Pfs48/45 are the leading candidates for malaria transmission-blocking vaccines. However, it remains unknown how the two interact and if additional domains in Pfs230 are potential vaccine candidates. Here we report a 3.36 Å resolution cryo-electron microscopy structure of the endogenous Pfs230-Pfs48/45 complex. We show that Pfs48/45 interacts with Pfs230 domains 13 and 14, which are distinct from domains included in current Pfs230 vaccine immunogens. Using a transgenic line with a domain 13 to 14 deletion, we show that these domains are essential for Pfs230 localization on the gamete surface. Nanobodies against these domains inhibit Pfs230-Pfs48/45 complex formation, reduce transmission and structural analyses reveal their binding epitopes. Pfs230 domains 13 and 14 are targets of naturally acquired immunity and when delivered as mRNA-LNP vaccines induced potent immune responses. Our comprehensive structural insights on a core P. falciparum fertilization complex guide the design of novel transmission-blocking vaccine candidates against malaria.
HostingRepository	PRIDE
AnnounceDate	2025-08-08
AnnouncementXML	Submission_2025-08-08_00:21:21.090.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Dagley
SpeciesList	scientific name: Plasmodium falciparum (isolate 3D7); NCBI TaxID: 36329;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse; timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-10 19:49:51	ID requested
⏵ 1	2025-08-08 00:21:21	announced

10.1126/science.ady0241;

Dietrich MH, Chmielewski J, Chan LJ, Tan LL, Adair A, Lyons FMT, Gabriela M, Lopaticki S, Dite TA, Dagley LF, Pazzagli L, Gupta P, Kamil M, Vaughan AM, Rojrung R, Abraham A, Mazhari R, Longley RJ, Zeglinski K, Gouil Q, Mueller I, Fabb SA, Shandre-Mugan R, Pouton CW, Glukhova A, Shakeel S, Tham WH, Pfs230 and Pfs48/45 fertilization complex. Science, 389(6765):eady0241(2025) [pubmed]

submitter keyword: transmission blocking, cryo-EM, Pfs48/45, vaccine, mRNA-LNP,malaria, nanobody, fertilization, Plasmodium falciparum, Pfs230

Wai-Hong Tham
contact affiliation	The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia
contact email	tham@wehi.edu.au
lab head
Laura Dagley
contact affiliation	WEHI
contact email	dagley.l@wehi.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/08/PXD060667

PRIDE project URI

• PRIDE
  1. PXD060667
     1. Label: PRIDE project
     2. Name: Cryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complex