Multiple Plasmodium falciparum Merozoite Surface Protein 1 Complexes Mediate Merozoite Binding to Human Erythrocytes

Hermann Bujard,Takafumi Tsuboi,Clara S Lin,Alessandro D Uboldi,Alan F Cowman,Christian Epp,Peter E Czabotar

doi:10.1074/jbc.m115.698282

Abstract

Successful invasion of human erythrocytes byPlasmodium falciparummerozoites is required for infection of the host and parasite survival. The early stages of invasion are mediated via merozoite surface proteins that interact with human erythrocytes. The nature of these interactions are currently not well understood, but it is known that merozoite surface protein 1 (MSP1) is critical for successful erythrocyte invasion. Here we show that the peripheral merozoite surface proteins MSP3, MSP6, MSPDBL1, MSPDBL2, and MSP7 bind directly to MSP1, but independently of each other, to form multiple forms of the MSP1 complex on the parasite surface. These complexes have overlapping functions that interact directly with human erythrocytes. We also show that targeting the p83 fragment of MSP1 using inhibitory antibodies inhibits all forms of MSP1 complexes and disrupts parasite growthin vitro.

Highlights

Invasion of merozoites into human erythrocytes is mediated through a series of interactions from distinct classes of proteins
The erythrocyte binding proteins MSPDBL1 and MSPDBL2 have been identified to be the most polymorphic antigens in the Plasmodium falciparum population, with most polymorphisms occurring in the DBL domain, suggesting that these molecules are under high selection pressure from the host immune system [35].Together, merozoite surface proteins (MSPs) appear to play significant roles in invasion, the exact function and mechanism through which these proteins act during invasion have not been clearly described
Processed Peripheral Merozoite Surface Proteins Are Incorporated onto the Surface of Merozoites Late in Schizogony—MSPs are processed during schizogony (Fig. 1A). 3D7 parasites were harvested at various stages of development during schizogony

Summary

Introduction

Invasion of merozoites into human erythrocytes is mediated through a series of interactions from distinct classes of proteins. We show that the peripheral merozoite surface proteins MSP3, MSP6, MSPDBL1, MSPDBL2, and MSP7 bind directly to MSP1, but independently of each other, to form multiple forms of the MSP1 complex on the parasite surface. The peripheral proteins MSPDBL1 and MSPDBL2 bind to MSP1 on the parasite surface and facilitate binding to red blood cells [17,18,19].

Results

Conclusion