HDP - A novel heme detoxification protein from the malaria parasite

被引:127
作者
Jani, Dewal [1 ]
Nagarkatti, Rana [1 ]
Beatty, Wandy [2 ]
Angel, Ross [3 ]
Slebodnick, Carla [4 ]
Andersen, John [5 ]
Kumar, Sanjai [6 ]
Rathore, Dharmendar [1 ]
机构
[1] Virginia Tech, Virgina Bioinformat Inst, Blacksburg, VA USA
[2] Washington Univ, Sch Med, St Louis, MO USA
[3] Virginia Tech, Dept Geosci, Blacksburg, VA USA
[4] Virginia Tech, Dept Chem, Blacksburg, VA USA
[5] Natl Inst Hlth, Lab Malaria & Vector Res, Rockville, MD USA
[6] US FDA, Bethesda, MD 20014 USA
关键词
D O I
10.1371/journal.ppat.1000053
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
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.
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页数:15
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