HDP—A Novel Heme Detoxification Protein from the Malaria Parasite

PLoS Pathogens

Carla Slebodnick¹  Ross Angel²  Sanjai Kumar³  John Andersen⁴  Dharmendar Rathore⁵  Dewal Jani⁵  Rana Nagarkatti⁵  Wandy Beatty⁶ 

[1] Department of Chemistry, Virginia Tech, Blacksburg, Virginia, United States of America;Department of Geosciences, Virginia Tech, Blacksburg, Virginia, United States of America;Food and Drug Administration, Bethesda, Maryland, United States of America;Laboratory of Malaria and Vector Research, National Institutes of Health, Rockville, Maryland, United States of America;Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America;Washington University School of Medicine, St. Louis, Missouri, United States of America

关键词: Heme;    Parasitic diseases;    Malarial parasites;    Plasmodium;    Hemoglobin;    Cytosol;    Vacuoles;    Yellow fluorescent protein;   

DOI  :  10.1371/journal.ppat.1000053

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

When malaria parasites infect host red blood cells (RBC) and proteolyze hemoglobin, a unique, albeit poorly understood parasite-specific mechanism, detoxifies released heme into hemozoin (Hz). Here, we report the identification and characterization of a novel Plasmodium Heme Detoxification Protein (HDP) that is extremely potent in converting heme into Hz. HDP is functionally conserved across Plasmodium genus and its gene locus could not be disrupted. Once expressed, the parasite utilizes a circuitous “Outbound–Inbound” trafficking route by initially secreting HDP into the cytosol of infected RBC. A subsequent endocytosis of host cytosol (and hemoglobin) delivers HDP to the food vacuole (FV), the site of Hz formation. As Hz formation is critical for survival, involvement of HDP in this process suggests that it could be a malaria drug target.

【 授权许可】

CC BY