National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R21 AI125983
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
T32 AI007323
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01 GM071940
米国
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)
R01 DE025567
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI094386
米国
National Institutes of Health/National Center for Research Resources (NIH/NCRR)
S10RR23057
米国
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
K99/R00 HL133453
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
U24GM116792
米国
National Institutes of Health/Office of the Director
S10OD018111
米国
National Science Foundation (NSF, United States)
DMR-1548924
米国
National Science Foundation (NSF, United States)
DBI-1338135
米国
引用
ジャーナル: Nature / 年: 2018 タイトル: Malaria parasite translocon structure and mechanism of effector export. 著者: Chi-Min Ho / Josh R Beck / Mason Lai / Yanxiang Cui / Daniel E Goldberg / Pascal F Egea / Z Hong Zhou / 要旨: The putative Plasmodium translocon of exported proteins (PTEX) is essential for transport of malarial effector proteins across a parasite-encasing vacuolar membrane into host erythrocytes, but the ...The putative Plasmodium translocon of exported proteins (PTEX) is essential for transport of malarial effector proteins across a parasite-encasing vacuolar membrane into host erythrocytes, but the mechanism of this process remains unknown. Here we show that PTEX is a bona fide translocon by determining structures of the PTEX core complex at near-atomic resolution using cryo-electron microscopy. We isolated the endogenous PTEX core complex containing EXP2, PTEX150 and HSP101 from Plasmodium falciparum in the 'engaged' and 'resetting' states of endogenous cargo translocation using epitope tags inserted using the CRISPR-Cas9 system. In the structures, EXP2 and PTEX150 interdigitate to form a static, funnel-shaped pseudo-seven-fold-symmetric protein-conducting channel spanning the vacuolar membrane. The spiral-shaped AAA+ HSP101 hexamer is tethered above this funnel, and undergoes pronounced compaction that allows three of six tyrosine-bearing pore loops lining the HSP101 channel to dissociate from the cargo, resetting the translocon for the next threading cycle. Our work reveals the mechanism of P. falciparum effector export, and will inform structure-based design of drugs targeting this unique translocon.