Myosin-like sequences in the malaria parasite Plasmodium falciparum bind human erythrocyte membrane protein 4.1

Department of Molecular Medicine and Haematology, National Health Laboratory Service, School of Pathology, University of the Witwatersrand, Parktown, Johannesburg 2193, South Africa. BACKGROUND AND OBJECTIVES: Plasmodium falciparum malaria is one of the most lethal infectious diseases afflicting humanity. During development within the erythrocyte, P. falciparum induces significant modifications to the structure and function of the human erythrocyte membrane. This study focused on the identification of new protein-protein interactions between host and parasite. DESIGN AND METHODS: A novel application of in vitro display technology was used: P. falciparum phage display expression libraries were screened against purified human erythrocyte protein 4.1. DNA sequencing and bioinformatic analyses were used to identify parasite proteins that bind protein 4.1. RESULTS: P. falciparum proteins displaying strong binding specificity toward protein 4.1 included five hypothetical proteins, erythrocyte binding antigen-175, erythrocyte binding ligand-1 like protein and a putative serine/threonine kinase. A common binding motif displaying homology to muscle myosin and neurofilament sequences was also identified in four of the eight proteins. INTERPRETATION AND CONCLUSIONS: These proteins are potentially involved in the invasion and/or release, as well as the growth and survival of malaria parasites during development with the red blood cell. The characterization of novel protein interactions between P. falciparum and erythrocyte membrane protein 4.1 will lead to a better understanding of malaria pathogenesis and parasite biology.