Native structure of the RhopH complex, a key determinant of malaria parasite nutrient acquisition
Chi-Min Ho, Jonathan Jih, Mason Lai, Xiaorun Li, Daniel E. Goldberg, Josh R. Beck, Z. Hong Zhou
Abstract
Significance Malaria parasites invade and replicate within human red blood cells, which lack nuclei and have minimal metabolic activity. To survive, the parasites create new pathways that alter the permeability of the red blood cell membrane, allowing them to import nutrients and export waste. Here, we present the native structure of the three-membered RhopH protein complex, which plays a key role in this process. We determined the structure of this essential complex from a heterogeneous mixture of proteins enriched directly from parasite cell lysate, using a cryo-electron microscopy–enabled endogenous structural proteomics approach. The native structure of the RhopH complex in a soluble, trafficking state helps elucidate the long-standing question of how parasite transmembrane proteins are trafficked to the erythrocyte membrane.