PKNH_0516100

PKNH_0516100 (TRAG40.1) is a Plasmodium knowlesi tryptophan-rich antigen implicated in erythrocyte attachment during infection (PMID:26393350). Recombinant PKNH_0516100 expressed in E. coli and CHO-K1 cells binds human erythrocytes in cell-ELISA and in vitro rosetting assays, and cross-competes with the P. knowlesi antigen PkTRAg38.3 and with P. vivax tryptophan-rich antigens for the same host erythrocyte receptor(s), indicating shared receptor usage among these tryptophan-rich antigens (PMID:26393350). Addition of the protein inhibits P. falciparum growth in vitro, consistent with a role in erythrocyte receptor–ligand interaction (PMID:26393350). Beyond this erythrocyte-binding characterization (PMID:26393350), no structural, mutagenesis, or in vivo mechanistic detail for PKNH_0516100 has been characterized in the available corpus, and the specific host receptor engaged remains unidentified.

1. 2015 Medium

   Establishing whether PKNH_0516100 engages host cells, this work showed the recombinant antigen binds human erythrocytes and shares receptor usage with other tryptophan-rich antigens, positioning it as a candidate ligand in erythrocyte attachment/invasion.

   Evidence cell-ELISA and in vitro rosetting with recombinant protein from E. coli and CHO-K1, cross-competition binding, and P. falciparum growth-inhibition assay

   PMID:26393350

   Open questions at the time

   • The specific human erythrocyte receptor bound is not identified
   • No structural or mutagenesis data defining the binding interface
   • Role in actual P. knowlesi invasion/growth demonstrated only indirectly via P. falciparum growth inhibition, not by direct genetic manipulation of the gene

• The molecular identity of the shared erythrocyte receptor and the physiological function of PKNH_0516100 during native P. knowlesi invasion remain unresolved.
• Host receptor unidentified
• No loss-of-function/genetic evidence in P. knowlesi
• No structural characterization of the binding domain