Related Experiment Videos
Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein
M J Blackman1, T J Scott-Finnigan, S Shai
1Division of Parasitology, National Institute for Medical Research, London, UK.
Abstract:
When merozoites of the malaria parasite Plasmodium falciparum are released from infected erythrocytes and invade new red cells, a component of a protein complex derived from the merozoite surface protein 1 (MSP-1) precursor undergoes a single proteolytic cleavage known as secondary processing. This releases the complex from the parasite surface, except for a small membrane-bound fragment consisting of two epidermal growth factor (EGF)-like domains, which is the only part of MSP-1 to be carried into invaded erythrocytes. We report that, a group of monoclonal antibodies specific for epitopes within the EGF-like domains, some interfere with secondary processing whereas others do not. Those that most effectively inhibit processing have previously been shown to prevent invasion. Other antibodies, some of which can block this inhibition, not only do not prevent invasion but are carried into the host cell bound to the merozoite surface. These observations unequivocally demonstrate that the binding of antibody to the COOH-terminal region of MSP-1 on the merozoite surface may not be sufficient to prevent erythrocyte invasion, and show that the interaction of different antibodies with adjacent epitopes within the EGF-like domains of MSP-1 can have distinct biochemical effects on the molecule. Inhibition of MSP-1 processing on merozoites may be a mechanism by which protective antibodies interrupt the asexual cycle of the malaria parasite.
Insights
Antibodies targeting the malaria parasite's merozoite surface protein 1 (MSP-1) can block its invasion of red blood cells by inhibiting a key processing step. This finding reveals how antibodies interrupt the malaria parasite's life cycle.
Area of Science:
- Malariology
- Immunology
- Molecular Parasitology
Background:
- The malaria parasite Plasmodium falciparum utilizes merozoites to infect red blood cells.
- Merozoite surface protein 1 (MSP-1) is crucial for parasite invasion and undergoes proteolytic processing.
- A fragment of MSP-1 containing epidermal growth factor (EGF)-like domains is the only part that enters the host cell.
Purpose of the Study:
- To investigate the role of specific antibodies targeting MSP-1's EGF-like domains in merozoite invasion.
- To determine how antibody binding affects MSP-1 secondary processing and parasite invasion.
Main Methods:
- Utilized monoclonal antibodies specific to epitopes within MSP-1's EGF-like domains.
- Assessed the impact of these antibodies on MSP-1 secondary processing.
- Evaluated antibody effects on Plasmodium falciparum merozoite invasion of erythrocytes.
Main Results:
- Some antibodies inhibited MSP-1 secondary processing and blocked merozoite invasion.
- Other antibodies, while binding to MSP-1, did not inhibit processing or invasion and were internalized.
- Distinct antibody interactions with adjacent epitopes on MSP-1 yielded different biochemical outcomes.
Conclusions:
- Antibody binding to the COOH-terminal region of MSP-1 is not sufficient to prevent erythrocyte invasion.
- Inhibiting MSP-1 processing on merozoites represents a potential mechanism for protective antibodies to disrupt the malaria parasite's asexual cycle.