PKNH_1324800 — Affinage

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PKNH_1324800 (TRAG38.3/PkTRAg38.3) is a Plasmodium knowlesi tryptophan-rich antigen implicated in host erythrocyte recognition during zoonotic infection (PMID:26393350). Recombinant PKNH_1324800, expressed in both E. coli and CHO-K1 cells, binds human erythrocytes as shown by cell-ELISA and in vitro rosetting, and cross-competes for erythrocyte receptor binding with PkTRAg40.1 and with P. vivax tryptophan-rich antigens (PvTRAgs), indicating shared receptor usage among these antigens (PMID:26393350). Recombinant PKNH_1324800 also inhibits P. falciparum growth in vitro, consistent with a receptor-ligand function at the erythrocyte surface (PMID:26393350). Beyond this erythrocyte-binding activity established in a single study (PMID:26393350), no further mechanistic detail — including the identity of its erythrocyte receptor, structural basis of binding, or in vivo function — has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step

2015 Medium
Whether PKNH_1324800 engages the host erythrocyte surface was unknown; demonstrating direct erythrocyte binding and shared receptor usage established it as a candidate ligand in P. knowlesi host-cell recognition.

Evidence Cell-ELISA with recombinant protein (E. coli and CHO-K1), in vitro rosetting, cross-competition binding, and in vitro P. falciparum growth inhibition in Plasmodium knowlesi

PMID:26393350
Open questions at the time
- The human erythrocyte receptor bound by PKNH_1324800 is not identified
- No mutagenesis or structural analysis defines the binding domain or specificity
- In vivo role during P. knowlesi infection and function distinct from PkTRAg40.1/PvTRAgs are not established

Open questions

Synthesis pass · forward-looking unresolved questions

The identity of the erythrocyte receptor, the structural basis of binding, and the native function of PKNH_1324800 during P. knowlesi blood-stage infection remain unresolved.
No receptor has been molecularly identified
No structural or mutagenesis data on the binding interface
No genetic or in vivo evidence for the antigen's role in invasion or sequestration

Mechanism profile

Synthesis pass · controlled-vocabulary classification

Partners

P. VIVAX TRYPTOPHAN-RICH ANTIGENS / PVTRAGS (SHARED ERYTHROCYTE RECEPTOR USAGE, BY CROSS-COMPETITION) [#0]PKTRAG40.1 (SHARED ERYTHROCYTE RECEPTOR USAGE, BY CROSS-COMPETITION) [#0]

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus

Year	Finding	Method	Journal	Conf	PMIDs
2015	PKNH_1324800 (PkTRAg38.3) binds to human erythrocytes, as demonstrated by cell-ELISA with recombinant protein expressed in E. coli and in mammalian CHO-K1 cells, and by in vitro rosetting assay. PkTRAg38.3 cross-competes for erythrocyte receptor binding with PkTRAg40.1 and with previously described P. vivax tryptophan-rich antigens (PvTRAgs), indicating shared receptor usage. Additionally, recombinant PkTRAg38.3 inhibited P. falciparum parasite growth in in vitro culture, further supporting a role in receptor-ligand interactions at the erythrocyte surface.	Cell-ELISA with recombinant protein (E. coli and CHO-K1 expression), in vitro rosetting assay, cross-competition binding assay, in vitro P. falciparum growth inhibition assay	PloS one	Medium	26393350

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations

Year	Title	Journal	Citations	PMID
2001	Properties of the Plasmodium falciparum homologue of a protective vaccine candidate of Plasmodium yoelii.	Molecular and biochemical parasitology	22	11704272
2015	A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate.	The Journal of biological chemistry	19	25960542
2008	Immunological responses to a 39.8kDa Plasmodium vivax tryptophan-rich antigen (PvTRAg39.8) among humans.	Microbes and infection	16	18603013
2011	Artesunate tolerance in transgenic Plasmodium falciparum parasites overexpressing a tryptophan-rich protein.	Antimicrobial agents and chemotherapy	15	21464256
2011	Plasmodium vivax tryptophan-rich antigen PvTRAg33.5 contains alpha helical structure and multidomain architecture.	PloS one	10	21283717
2015	Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi.	PloS one	9	26393350
2022	A member of the tryptophan-rich protein family is required for efficient sequestration of Plasmodium berghei schizonts.	PLoS pathogens	8	36126089
2022	Genetic Diversity and Phylogenetic Relatedness of Plasmodium ovale curtisi and Plasmodium ovale wallikeri in sub-Saharan Africa.	Microorganisms	1	35744665
2026	Transcriptomics of Plasmodium vivax rosetting.	Memorias do Instituto Oswaldo Cruz	0	41810678
2026	Poly(I:C) and R848 adjuvants elicit sizeable humoral immunity to liver stage malaria antigens.	Frontiers in immunology	0	41983137