Characterization of the malaria parasite protein PfTip, a novel invasion-related protein

Abstract

Malaria is one of the most common infective diseases in the world. Invasion of host erythrocytes by the malaria parasite is crucial for pathogen survival and pathogenesis. Various proteins mediate parasite invasion and identification of novel invasion-related proteins may aid in elucidating the underlying molecular mechanism and new intervention strategies for malaria control. This study characterized the PfTip protein, a homolog of the human T‑cell immunomodulatory protein, and examined its function in preventing parasite infection. Bioinformatics analysis and experimental validation were adopted in the present study. Bioinformatics analysis showed that PfTip has a β‑propeller fold in its structure and is highly expressed at the early ring stage. TNFRSF14 was predicted to be a candidate interactant of PfTip. Further analyses showed that PfTip blockage by sera inhibited erythrocyte invasion by the malaria parasite. The protective effect of PfTip was further confirmed through in vivo analysis. To the best of our knowledge, this study is the first to provide evidence on the function of PfTip in erythrocyte parasite invasion. Additional assays involving the receptor of this protein are currently underway.

A Single-Pass Type I Membrane Protein from the Apicomplexan Parasite Cryptosporidium parvum with Nanomolar Binding Affinity to Host Cell Surface

“…TIPHs and ITGA homologs are widely present in eukaryotes [ 24 , 25 , 26 ], while VCBS repeat is present at high copy numbers in some species of the bacterial Vibrio, Colwellia, Bradyrhizobium and Shewanella (InterPro domain IPR010221) [ 27 ]. TIPHs, ITGA and VBSC repeat are known for their adhesion property involved in cell-to-cell interactions and have been identified in other apicomplexan parasites (e.g., Toxoplasma and Plasmodium ) for their potential involvement in the attachment and invasion of parasites into host cells [ 25 , 26 , 28 , 29 ]. In the present study, we experimentally confirmed the binding affinity of the N-terminal half of the CpTIPH to host cells, and observed low nanomolar K d binding affinity, suggesting that CpTIPH is an excellent cell surface binding protein.…”