Plasmodium knowlesi tryptophan-rich antigen 40.1 binds human erythrocyte spectrin alpha.

Authors

Wang-Jong Lee, Fadhila Fitriana, Jadidan Hada Syahada, Johnsy Mary Louis, Hyun-Young Sim, Ernest Mazigo, Hojong Jun, Fauzi Muh, Feng Lu, Seok Ho Cha, Se Jin Lee, Sunghun Na, Wanjoo Chun, Won Sun Park, Yee Ling Lau, Robert W Moon, Eun-Taek Han, Jin-Hee Han

Published in

PLoS neglected tropical diseases. Volume 20. Issue 9. Pages e0014700. Epub Sep 17, 2026.

Abstract

Plasmodium infection induces extensive remodeling of host erythrocytes through parasite-exported proteins that interact with host cell components. Among these, tryptophan-rich antigens (TRAgs) are conserved across Plasmodium species and have been proposed as vaccine candidates, but their molecular functions remain largely unexplored. In this study, we characterized Plasmodium knowlesi tryptophan-rich antigen 40.1 (PkTRAg40.1) to investigate its localization, biochemical properties, host interactions, and immunogenicity. Recombinant PkTRAg40.1 showed no detectable binding to intact human erythrocytes in flow cytometry-based binding assays. Biochemical characterization demonstrated that native PkTRAg40.1 was predominantly associated with detergent-resistant insoluble fractions and was detected as multiple higher-molecular-weight forms. Protease protection assays further showed that native PkTRAg40.1 was accessible to protease under the experimental conditions tested. Consistent with these observations, immunofluorescence assays revealed that PkTRAg40.1 colocalized with skeleton-binding protein 1 (PkSBP1), supporting its localization to Sinton and Mulligan's clefts (SMCs), parasite-derived membranous structures. Pull-down assays and MALDI-TOF/MS identified spectrin alpha as a host binding partner, and biolayer interferometry confirmed its specific interaction with the spectrin alpha α12-16 fragment (KD = 4.71 ± 0.62 μM). Serological analysis of P. knowlesi patient samples revealed that PkTRAg40.1 is immunogenic, exhibiting 50% sensitivity and 92.9% specificity, and also displayed cross-reactivity with sera from Plasmodium vivax-infected patients. Collectively, these findings identify PkTRAg40.1 as a TRAg associated with parasite-derived membranous structures that interacts with the host erythrocyte cytoskeleton, thereby expanding current understanding of the molecular functions of Plasmodium TRAgs.

PMID:
42752678
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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